Search

Your search keyword '"Massimiliano Rossi"' showing total 375 results
Start Over Author "Massimiliano Rossi"
375 results on '"Massimiliano Rossi"'

251. Uncommon nucleotide excision repair phenotypes revealed by targeted high-throughput sequencing

Author

Massimiliano Rossi, Boris Keren, François Feillet, Julien Tarabeux, Isabel Llano-Rivas, Florence Renaldo-Robin, Vincent Laugel, Patricia Bretones, Bérénice Doray, Marguerite Miguet, Géraldine Greff, Caroline Michot, Béatrice Digeon, Nadine Kempf, Nadège Calmels, Anne Cavau, Martine Doco-Fenzy, Claire Gasnier, Cathy Obringer, Jean-Louis Mandel, Pascal Sabouraud, Jesus Gardeazabal, Didier Bessis, Christel Depienne, Blanca Gener, Artur Mazur, Jean Muller, Sophie Julia, Geneviève Baujat, Laboratoire de Diagnostic Génétique, CHU Strasbourg-Hopital Civil, Laboratoire de Génétique Médicale (LGM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'endocrinologie pédiatrique, Hôpital mère enfant, Bron, CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Universitaire de Reims (CHU Reims), Centre hospitalier Félix-Guyon [Saint-Denis, La Réunion], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), BioCruces Research Institute, University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU)-Hospital Universitario Cruces = Cruces University Hospital, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Rzeszow University, Unité de Neurologie, Hôpital Robert Debré, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Collège de France - Chaire Génétique Humaine, Collège de France (CdF (institution)), CHU Strasbourg, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Saint-Eloi, University of the Basque Country [Bizkaia] (UPV/EHU)-Hospital Universitario Cruces = Cruces University Hospital, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de génétique, cytogénétique, embryologie [Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Chaire Génétique Humaine, CHU Strasbourg - Hopital Civil, Laboratoire de Génétique Médicale, Université de Strasbourg - Institut National de la Santé et de la Recherche Médicale (INSERM) - Faculté de Médecine, Centre de référence maladies osseuses constitutionnelles CHU Necker, Hôpital Necker - Enfants malades, Assistance publique - Hôpitaux de Paris (AP-HP) - Université Paris Descartes - Paris 5 (UPD5), CHU Reims, CHU Félix Guyon, Université de Lorraine (UL) - Institut National de la Santé et de la Recherche Médicale (INSERM), University of the Basque Country [Bizkaia] (UPV/EHU) - Cruces University Hospital, Hôpital Purpan, Hospices Civils de Lyon / Centre hospitalier Lyon Sud (HCL), Hospices Civils de Lyon, Centre de recherche en neurosciences de Lyon, Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université Claude Bernard Lyon 1 (UCBL) - Université Jean Monnet - Saint-Etienne - PRES Université de Lyon, Université Pierre et Marie Curie - Paris 6 (UPMC) - Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Pitié-Salpêtrière [APHP], Institut du Cerveau et de la Moëlle Epinière (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC) - Institut National de la Santé et de la Recherche Médicale (INSERM) - CHU Pitié-Salpêtrière [APHP] - Centre National de la Recherche Scientifique (CNRS), Service de génétique, cytogénétique, embryologie [CHU Pitié-Salpétrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and HAL UPMC, Gestionnaire

Subjects
0301 basic medicine, ERCC6, ERCC8, DNA Repair, DNA-Directed DNA Polymerase, Cockayne syndrome, Genetics(clinical), Pharmacology (medical), Poly-ADP-Ribose Binding Proteins, Genetics (clinical), Medicine(all), Genetics, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, High-Throughput Nucleotide Sequencing, Nuclear Proteins, General Medicine, 3. Good health, DNA-Binding Proteins, Phenotype, POLH, NGS, Xeroderma pigmentosum, Population, Single-nucleotide polymorphism, Biology, 03 medical and health sciences, medicine, Humans, education, Xeroderma Pigmentosum Group D Protein, Research, DNA Helicases, xeroderma pigmentosum, medicine.disease, Endonucleases, 030104 developmental biology, DNA Repair Enzymes, Mutation, NER, ERCC2, ERCC3, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Nucleotide excision repair, Transcription Factors, ERCC5
Abstract

Background Deficient nucleotide excision repair (NER) activity causes a variety of autosomal recessive diseases including xeroderma pigmentosum (XP) a disorder which pre-disposes to skin cancer, and the severe multisystem condition known as Cockayne syndrome (CS). In view of the clinical overlap between NER-related disorders, as well as the existence of multiple phenotypes and the numerous genes involved, we developed a new diagnostic approach based on the enrichment of 16 NER-related genes by multiplex amplification coupled with next-generation sequencing (NGS). Methods Our test cohort consisted of 11 DNA samples, all with known mutations and/or non pathogenic SNPs in two of the tested genes. We then used the same technique to analyse samples from a prospective cohort of 40 patients. Multiplex amplification and sequencing were performed using AmpliSeq protocol on the Ion Torrent PGM (Life Technologies). Results We identified causative mutations in 17 out of the 40 patients (43 %). Four patients showed biallelic mutations in the ERCC6(CSB) gene, five in the ERCC8(CSA) gene: most of them had classical CS features but some had very mild and incomplete phenotypes. A small cohort of 4 unrelated classic XP patients from the Basque country (Northern Spain) revealed a common splicing mutation in POLH (XP-variant), demonstrating a new founder effect in this population. Interestingly, our results also found ERCC2(XPD), ERCC3(XPB) or ERCC5(XPG) mutations in two cases of UV-sensitive syndrome and in two cases with mixed XP/CS phenotypes. Conclusions Our study confirms that NGS is an efficient technique for the analysis of NER-related disorders on a molecular level. It is particularly useful for phenotypes with combined features or unusually mild symptoms. Targeted NGS used in conjunction with DNA repair functional tests and precise clinical evaluation permits rapid and cost-effective diagnosis in patients with NER-defects. Electronic supplementary material The online version of this article (doi:10.1186/s13023-016-0408-0) contains supplementary material, which is available to authorized users.

Published
2016

253. Targeted resequencing identifies PTCH1 as a major contributor to ocular developmental anomalies and extends the SOX2 regulatory network

Author

Nicolas Chassaing, Josseline Kaplan, Catherine Vincent-Delorme, Adrienne R. Niederriter, Sophie Lamarre, Stanislas Faguer, Nicholas Katsanis, Kelly L. McKnight, Erica E. Davis, Didier Lacombe, Annaïck Desmaison, Jean-Louis Dufier, Massimiliano Rossi, Christine Coubes, Laurent Pasquier, Heather C. Etchevers, Alexandre Causse, Hélène Dollfus, Patrick Calvas, Véronique David, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de biologie moléculaire, Hôpital Pontchaillou, Institut des Technologies Avancées en sciences du Vivant (ITAV), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Centre de Maladies Rares, Anomalies du Développement Nord de France-CH Arras - CHRU Lille, CHU Pontchaillou [Rennes], Service de Génétique Clinique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'ophtalmologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Référence pour les Affections Rares en Génétique Ophtalmologique (CARGO) et Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Center for Human Disease Modeling, Duke University [Durham], Département de Néphrologie et Transplantation d'organes, Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Centre de référence des maladies rénales rares, CHU Toulouse [Toulouse]-Hôpital de Rangueil, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), PHRC 09 109 01, Clinical Research Hospital Program from the French Ministry of Health, Retina France, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Duke University Medical Center, Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Référence du sud-Ouest des maladies rénales rares [CHU Toulouse] (SODARE), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse, Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut des Technologies Avancées en sciences du Vivant ( ITAV ), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés ( LISBP ), Institut National de la Recherche Agronomique ( INRA ) -Institut National des Sciences Appliquées - Toulouse ( INSA Toulouse ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Université de Bordeaux ( UB ) -CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Inserm U1028, équipe TIGER, Centre de recherche en neurosciences de Lyon ( CRNL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Service de Génétique, Hospices Civils de Lyon ( HCL ) -Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Groupe Hospitalier Est-Hospices Civils de Lyon ( HCL ) -Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon ( HCL ) -Groupe Hospitalier Est, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Duke university [Durham], Institut des Maladies Métaboliques et Cardiovasculaires ( I2MC ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital de Rangueil, and CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier ( UPS )

Subjects
0301 basic medicine, Patched, Candidate gene, Heterozygote, endocrine system, Biology, Microphthalmia, Frameshift mutation, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, medicine, Missense mutation, Animals, Humans, Gene Regulatory Networks, Eye Abnormalities, Sonic hedgehog, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Genetics (clinical), Alleles, Zebrafish, Anophthalmia, [ SDV ] Life Sciences [q-bio], SOXB1 Transcription Factors, Research, Sequence Analysis, DNA, medicine.disease, Patched-1 Receptor, Disease Models, Animal, 030104 developmental biology, Phenotype, PTCH1, Gene Expression Regulation, Genetic Loci, Case-Control Studies, Mutation, embryonic structures, biology.protein
Abstract

Ocular developmental anomalies (ODA) such as anophthalmia/microphthalmia (AM) or anterior segment dysgenesis (ASD) have an estimated combined prevalence of 3.7 in 10,000 births. Mutations in SOX2 are the most frequent contributors to severe ODA, yet account for a minority of the genetic drivers. To identify novel ODA loci, we conducted targeted high-throughput sequencing of 407 candidate genes in an initial cohort of 22 sporadic ODA patients. Patched 1 (PTCH1), an inhibitor of sonic hedgehog (SHH) signaling, harbored an enrichment of rare heterozygous variants in comparison to either controls, or to the other candidate genes (four missense and one frameshift); targeted resequencing of PTCH1 in a second cohort of 48 ODA patients identified two additional rare nonsynonymous changes. Using multiple transient models and a CRISPR/Cas9-generated mutant, we show physiologically relevant phenotypes altering SHH signaling and eye development upon abrogation of ptch1 in zebrafish for which in vivo complementation assays using these models showed that all six patient missense mutations affect SHH signaling. Finally, through transcriptomic and ChIP analyses, we show that SOX2 binds to an intronic domain of the PTCH1 locus to regulate PTCH1 expression, findings that were validated both in vitro and in vivo. Together, these results demonstrate that PTCH1 mutations contribute to as much as 10% of ODA, identify the SHH signaling pathway as a novel effector of SOX2 activity during human ocular development, and indicate that ODA is likely the result of overactive SHH signaling in humans harboring mutations in either PTCH1 or SOX2.

Published
2016

254. Microfluidic Chip for Generating Gradient Polymer Films for Biological Applications

Author

Massimiliano Rossi, Christian J. Kähler, Pavel A. Levkin, Junsheng Li, Ludmilla Popp, Rodrigo Segura, Andreas E. Guber, and Kristina Kreppenhofer

Subjects
chemistry.chemical_classification, Materials science, Micromixer, Nanotechnology, General Medicine, Polymer, Adhesion, Polymerization, Microfluidic chip, Biological surface, chemistry, Gradient, Engineering(all)
Abstract

The behavior of cells, like adhesion or differentiation in case of stem cells, is influenced by the surface the cells are cultivated on. Cells sense the actual properties of the surface as well as gradients of these properties. Here we present the production and usage of a microfluidic chip for generating polymer films possessing gradients of morphology. The polymer surface's properties are defined by the composition of the polymerization mixtures injected into the microfluidic chip. After polymerization and subsequent removal of one part of the microfluidic chip, the surface of the gradient films is accessible for biological experiments on glass slides.

Published
2012
Full Text
View/download PDF

255. Recurrent Dominant Mutations Affecting Two Adjacent Residues in the Motor Domain of the Monomeric Kinesin KIF22 Result in Skeletal Dysplasia and Joint Laxity

Author

Sebastian Kalamajski, H. Rosemarie Davidson, A. Belinda Campos-Xavier, Eugênia Ribeiro Valadares, Goranka Tanackovich, Andrea Superti-Furga, Christine Hall, Daniel H. Cohn, Massimiliano Rossi, Generoso Andria, R. Curtis Rogers, Shiro Ikegawa, Diana Ballhausen, André Mégarbané, Michael D. Briggs, Sheila Unger, David L. Rimoin, Claire L. Hartley, Rainer König, Richard H Scott, Luisa Bonafé, Ralph S. Lachman, Eric D. Boyden, John F. Bateman, Pierre-Simon Jouk, Geert Mortier, Philippe Suarez, Trevor L. Cameron, Matthew L. Warman, Hirotake Sawada, Gen Nishimura, Boyden, Ed, Campos Xavier, Ab, Kalamajski, S, Cameron, Tl, Suarez, P, Tanackovic, G, Andria, Generoso, Ballhausen, D, Briggs, Md, Hartley, C, Cohn, Dh, Davidson, Hr, Hall, C, Ikegawa, S, Jouk, P, König, R, Megarbané, A, Nishimura, G, Lachman, R, Mortier, G, Rimoin, Dl, Rogers, Rc, Rossi, M, Sawada, H, Scott, R, Unger, S, Valadares, Er, Bateman, Jf, Warman, Ml, Superti Furga, A, Bonafé, L., and Tanackovich, G

Subjects
Male, Joint Dislocations, Gene Expression, Kinesins, Joint laxity, Motor domain, Mice, 0302 clinical medicine, Missense mutation, Exome, Genetics(clinical), Growth Plate, Child, Cells, Cultured, Genetics (clinical), Genes, Dominant, Genetics, 0303 health sciences, Chemistry, Joint Laxity, Monomeric Kinesin KIF22, Phenotype, Cell biology, DNA-Binding Proteins, Kinesin, Erratum, Joint Instability, Skeletal Dysplasia, Mutation, Missense, Biology, Osteochondrodysplasias, 03 medical and health sciences, Skeletal disorder, Report, medicine, Animals, Humans, Abnormalities, Multiple, Amino Acid Sequence, Genetic Association Studies, 030304 developmental biology, Spondyloepimetaphyseal dysplasia, Base Sequence, Tibia, Sequence Analysis, DNA, medicine.disease, Protein Structure, Tertiary, Dysplasia, Human medicine, 030217 neurology & neurosurgery
Abstract

Spondyloepimetaphyseal dysplasia with joint laxity, leptodactylic type (lepto-SEMDJL, aka SEMDJL, Hall type), is an autosomal dominant skeletal disorder that, in spite of being relatively common among skeletal dysplasias, has eluded molecular elucidation so far. We used whole-exome sequencing of five unrelated individuals with lepto-SEMDJL to identify mutations in KIF22 as the cause of this skeletal condition. Missense mutations affecting one of two adjacent amino acids in the motor domain of KIF22 were present in 20 familial cases from eight families and in 12 other sporadic cases. The skeletal and connective tissue phenotype produced by these specific mutations point to functions of KIF22 beyond those previously ascribed functions involving chromosome segregation. Although we have found Kif22 to be strongly upregulated at the growth plate, the precise pathogenetic mechanisms remain to be elucidated.

Published
2011

256. A comparative analysis of the uncertainty of astigmatism-μPTV, stereo-μPIV, and μPIV

Author

Massimiliano Rossi, Christian Cierpka, Christian J. Kähler, Rodrigo Segura, and Francesco Mastrangelo

Subjects
Fluid Flow and Transfer Processes, Wavefront, business.industry, Computer science, Computational Mechanics, General Physics and Astronomy, Stereoscopy, Physics and Astronomy(all), Astigmatism, Velocimetry, medicine.disease, Tracking (particle physics), law.invention, Optics, Mechanics of Materials, Particle tracking velocimetry, law, medicine, Calibration, Measurement uncertainty, business
Abstract

Astigmatism or wavefront deformation, microscopic particle tracking velocimetry (A-μPTV) (Chen et al. in Exp Fluids 47:849–863, 2009; Cierpka et al. in Meas Sci Technol 21:045401, 2010b) is a method to determine the complete 3D3C velocity field in micro-fluidic devices with a single camera. By using an intrinsic calibration procedure that enables a robust and precise calibration on the basis of the measured data itself (Cierpka et al. in Meas Sci Technol 22:015401, doi: 10.1088/0957-0233/22/1/015401 , 2011), accurate results without errors due to spatial averaging or bias due to the depth of correlation can be obtained. This method takes all image aberrations into account, allows for the use of the whole CCD sensor, and is easy to apply without expert knowledge. In this paper, a comparative study is presented to assess the uncertainties of two state-of-the-art methods for 3C3D velocity field measurements in microscopic flows: stereoscopic micro-particle image velocimetry (S-μPIV) and astigmatism micro-particle tracking velocimetry (A-μPTV). First, the main parameters affecting all methods’ measurement uncertainty are identified, described, and quantified. Second, the test case of the flow over a backward-facing step is analyzed using all methods. For comparison, standard 2D2C μPIV measurements and numerical flow simulations are shown as well. Advantages and disadvantages of both methods are discussed.

Published
2011

257. Clogging in constricted suspension flows

Author

Henri Lhuissier, Massimiliano Rossi, Alvaro Marin, Christian J. Kähler, Institut universitaire des systèmes thermiques industriels (IUSTI), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Hospices Civils de Lyon (HCL), Institute for Fluidmechanics and Aerodynamics (IFA), Universität der Bundeswehr München [Neubiberg], Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), and Physics of Fluids

Subjects
Materials science, Flow (psychology), Fluid Dynamics (physics.flu-dyn), FOS: Physical sciences, 02 engineering and technology, Mechanics, Physics - Fluid Dynamics, Condensed Matter - Soft Condensed Matter, 021001 nanoscience & nanotechnology, Tracking (particle physics), 01 natural sciences, law.invention, Clogging, Physics::Fluid Dynamics, law, 0103 physical sciences, Lubrication, Particle, Soft Condensed Matter (cond-mat.soft), Size ratio, Hourglass, [PHYS.MECA.MEFL]Physics [physics]/Mechanics [physics]/Fluid mechanics [physics.class-ph], 010306 general physics, 0210 nano-technology, Suspension (vehicle)
Abstract

International audience; The flow of a charged-stabilized suspension through a single constricted channel is studied experimentally by tracking the particles individually. Surprisingly, the behavior is found to be qualitatively similar to that of inertial dry granular systems: For small values of the neck-to-particle size ratio (D/d < 3), clogs form randomly as arches of the particle span the constriction. The statistics of the clogging events are Poissonian as reported for granular systems and agree for moderate particle volume fraction (φ ≈ 20%) with a simple stochastic model for the number of particles at the neck. For larger neck sizes (D/d > 3), even at the largest φ (≈ 60%) achievable in the experiments, an uninterrupted particle flow is observed, which resembles that of an hourglass. This particularly small value of D/d (3) at the transition to a practically uninterrupted flow is attributed to the low effective friction between the particles, achieved by the particle's functionalization and lubrication.

Published
2018

258. A large-scale mutation search reveals genetic heterogeneity in 3M syndrome

Author

Arnold Munnich, Fabien Guimiot, H. Plauchu, Maria-Luisa Giovannucci-Uzielli, Patrick Edery, Anee-Lise Delezoide, Luitgard Graul-Neumann, Massimiliano Rossi, Carl-Joachim Partsch, Valérie Malan, Judith Melki, Pierre Chatelain, Thomas Edouard, Kate Gibson, Robin D. Clark, Martin Zenker, Helen Stewart, Johana-Maria van Hagen, Liselot P. van Hest, Gabriele Gillessen-Kaesbach, Clarisse Baumann, Martine Le Merrer, Helen Cox, Anna Rajab, Carol Chu, Elisabeth Steichen-Gersdorf, Valérie Cormier-Daire, Céline Huber, Dominique Bonneau, Daniela Bezerra Da Silva, Virginia Fano, Sheila Unger, Dafne Horovitz, David Sillence, Human genetics, and Other Research

Subjects
Male, Short Report, Genes, Recessive, Locus (genetics), Consanguinity, Biology, Genetic Heterogeneity, Fetus, Genetics, medicine, Humans, Abnormalities, Multiple, Family, Child, Gene, Genetics (clinical), Isodisomy, Genetic diversity, Fetal Growth Retardation, Genetic heterogeneity, Postnatal growth retardation, Syndrome, Cullin Proteins, medicine.disease, Radiography, Child, Preschool, Mutation, 3-M syndrome
Abstract

The 3M syndrome is a rare autosomal recessive disorder recently ascribed to mutations in the CUL7 gene and characterized by severe pre- and postnatal growth retardation. Studying a series of 33 novel cases of 3M syndrome, we have identified deleterious CUL7 mutations in 23/33 patients, including 19 novel mutations and one paternal isodisomy of chromosome 6 encompassing a CUL7 mutation. Lack of mutations in 10/33 cases and exclusion of the CUL7 locus on chromosome 6p21.1 in six consanguineous families strongly support the genetic heterogeneity of the 3M syndrome.

Published
2008

259. Pharmacological Enhancement of Mutated α-Glucosidase Activity in Fibroblasts from Patients with Pompe Disease

Author

M Gabriela Pittis, Andrea Ballabio, Francesca Donaudy, Germana Meroni, Alice Donati, Barbara Rossi, Caterina Porto, Alfredo Zuppaldi, Mirella Filocamo, Massimiliano Rossi, Bruno Bembi, Generoso Andria, Giancarlo Parenti, M Rosaria Tuzzi, Ida Annunziata, Parenti, G, Zuppaldi, A, Pittis, Mg, Tuzzi, Mr, Annunziata, I, Meroni, Germana, Porto, C, Donaudy, F, Rossi, B, Rossi, M, Filocamo, M, Donati, A, Bembi, B, Ballabio, A, Andria, G., Parenti, Giancarlo, Zuppaldi, Alfredo, GABRIELA PITTIS, M, Meroni, G, Ballabio, Andrea, and Andria, Generoso

Subjects
Adult, congenital, hereditary, and neonatal diseases and abnormalities, Genotype, Metabolic myopathy, Biology, medicine.disease_cause, Cell Line, lysosomal hydrolase alpha-glucosidase, chemistry.chemical_compound, Western blot, Drug Discovery, Genetics, medicine, Humans, Child, Molecular Biology, Pharmacology, chemistry.chemical_classification, Mutation, Glycogen, medicine.diagnostic_test, Glycogen Storage Disease Type II, HEK 293 cells, Pompe disease, nutritional and metabolic diseases, Skeletal muscle, alpha-Glucosidases, Fibroblasts, medicine.disease, Molecular biology, Imino Sugars, Enzyme Activation, Pompe disease, lysosomal hydrolase alpha-glucosidase, imino sugars, Phenotype, Enzyme, medicine.anatomical_structure, chemistry, Cell culture, Child, Preschool, Molecular Medicine, Female
Abstract

We investigated the use of pharmacological chaperones for the therapy of Pompe disease, a metabolic myopathy due to mutations of the gene encoding the lysosomal hydrolase alpha-glucosidase (GAA) and characterized by generalized glycogen storage in cardiac and skeletal muscle. We studied the effects of two imino sugars, deoxynojirimycin (DNJ) and N-butyldeoxynojirimycin (NB-DNJ), on residual GAA activity in fibroblasts from eight patients with different forms of Pompe disease (two classic infantile, two non-classic infantile onset, four late-onset forms), and with different mutations of the GAA gene. We demonstrated a significant increase of GAA activity (1.3-7.5-fold) after imino sugar treatment in fibroblasts from patients carrying the mutations L552P (three patients) and G549R (one patient). GAA enhancement was confirmed in HEK293T cells where the same mutations were overexpressed. No increase of GAA activity was observed for the other mutations. Western blot analysis showed that imino sugars increase the amount of mature GAA molecular forms. Immunofluorescence studies in HEK293T cells overexpressing the L552P mutation showed an improved trafficking of the mutant enzyme to lysosomes after imino sugar treatment. These results provide a rationale for an alternative treatment, other than enzyme replacement, to Pompe disease.

Published
2007

260. Surfactant-driven flow transitions in evaporating droplets

Author

Robert Liepelt, Christian J. Kähler, Alvaro Marin, and Massimiliano Rossi

Subjects
Surface (mathematics), Materials science, Flow (psychology), Fluid Dynamics (physics.flu-dyn), FOS: Physical sciences, 02 engineering and technology, General Chemistry, Mechanics, Physics - Fluid Dynamics, 010402 general chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Tracking (particle physics), 01 natural sciences, Surface energy, 0104 chemical sciences, Surface tension, Physics::Fluid Dynamics, Pulmonary surfactant, Fluid dynamics, Particle, 0210 nano-technology
Abstract

An evaporating droplet is a dynamic system in which flow is spontaneously generated to minimize the surface energy, dragging particles to the borders and ultimately resulting in the so-called "coffee-stain effect". The situation becomes more complex at the droplet's surface, where surface tension gradients of different nature can compete with each other yielding different scenarios. With careful experiments and with the aid of 3D particle tracking techniques, we are able to show that different types of surfactants turn the droplet's surface either rigid or elastic, which alters the evaporating fluid flow, either enhancing the classical coffee-stain effect or leading to a total flow inversion. Our measurements lead to unprecedented and detailed measurements of the surface tension difference along an evaporating droplet's surface with good temporal and spatial resolution., Accepted for publication in Soft Matter (RSC)

Published
2015

261. Growth control of sessile microbubbles in PDMS devices

Author

Andreas Volk, Christian J. Kähler, Sascha Hilgenfeldt, Alvaro Marin, and Massimiliano Rossi

Subjects
Materials science, Polydimethylsiloxane, Vapor pressure, Bubble, Hydrostatic pressure, Microfluidics, Fluid Dynamics (physics.flu-dyn), Biomedical Engineering, FOS: Physical sciences, Bioengineering, 02 engineering and technology, General Chemistry, Mechanics, Physics - Fluid Dynamics, 021001 nanoscience & nanotechnology, 01 natural sciences, Biochemistry, 010305 fluids & plasmas, chemistry.chemical_compound, chemistry, Cavitation, 0103 physical sciences, Microbubbles, 0210 nano-technology, Shrinkage
Abstract

In a microfluidic environment, the presence of bubbles is often detrimental to the functionality of the device, leading to clogging or cavitation, but microbubbles can also be an indispensable asset in other applications such as microstreaming. In either case, it is crucial to understand and control the growth or shrinkage of these bodies of air, in particular in common soft-lithography devices based on polydimethylsiloxane (PDMS), which is highly permeable to gases. In this work, we study the gas transport into and out of a bubble positioned in a microfluidic device, taking into account the direct gas exchange through PDMS as well as the transport of gas through the liquid in the device. Hydrostatic pressure regulation allows for the quantitative control of growth, shrinkage, or the attainment of a stable equilibrium bubble size. We find that the vapor pressure of the liquid plays an important role for the balance of gas transport, accounting for variability in experimental conditions and suggesting additional means of bubble size control in applications., 6 pages, supplementary information and cover included in ancillary files

Published
2015

262. Fabrication and testing of STREEGO: a compact optical payload for earth observation on small satellites

Author

Riccardo Ghislanzoni, Matteo Taccola, Massimiliano Rossi, Piet Holbrouck, A. Ritucci, Fabio Zocchi, Ivan Ferrario, and Marco Terraneo

Subjects
Engineering, Earth observation, Optics, business.industry, Aperture, Payload, Ground sample distance, Field of view, Three-mirror anastigmat, Nyquist frequency, Large format, business, Remote sensing
Abstract

In the framework of an European Space Agency contract, Media Lario Technologies is developing an optical payload for Earth Observation targeted to small satellites. In this paper we present a detailed description of the imager which, by leveraging on aspheric surfaces, bonnet polishing, lightweight materials, an off-the-shelf large format CMOS detector and multispectral filters integrated in the FPA, achieves remarkable image quality with compact volume claim and mass of only 15 kg. The instrument is based on a three mirror anastigmat (TMA) design with an aperture of 200 mm and an F/number of 6. The payload is designed to provide a ground sampling distance (GSD) of 2.75 m for the panchromatic channel at a reference altitude of 600 km, a field of view of 1° and a nominal MTF greater than 60% at Nyquist frequency with a Signal to Noise Ratio (SNR) greater than 100.

Published
2015

263. Radiographic features of the skeleton in disorders of post-squalene cholesterol biosynthesis

Author

Christine Hall, Massimiliano Rossi, Patrick Edery, Giancarlo Parenti, Christine Vianey-Saban, Generoso Andria, Sophie Collardeau-Frachon, Frédérique Le Breton, Martine Bucourt, Amaka C. Offiah, Marie Pierre Cordier, Raymonde Bouvier, Martine Le Merrer, Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Rossi, Massimiliano, Hall, Christine M, Bouvier, Raymonde, Collardeau Frachon, Sophie, Le Breton, Frédérique, Bucourt, Martine, Cordier, Marie Pierre, Vianey Saban, Christine, Parenti, Giancarlo, Andria, Generoso, Le Merrer, Martine, Edery, Patrick, and Offiah, Amaka C.

Subjects
Prenatal Diagnosi, Male, [SDV]Life Sciences [q-bio], Lipid Metabolism, Inborn Error, Musculoskeletal System/*radiography, Musculoskeletal Abnormalities/*complications/*radiography, Pregnancy, Prenatal Diagnosis, Chondrodysplasia punctata, Child, Musculoskeletal System, 0303 health sciences, Rhizomelic chondrodysplasia punctata, Polydactyly, 030305 genetics & heredity, Cholesterol/*biosynthesis, Lathosterolosis, CHILD syndrome, 3. Good health, Cholesterol, Child, Preschool, Female, Human, musculoskeletal diseases, Adult, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Inborn Errors/*complications, Lipid Metabolism, Inborn Errors, Musculoskeletal Abnormalitie, 03 medical and health sciences, Young Adult, Internal medicine, Peroxisomal disorder, medicine, Humans, Radiology, Nuclear Medicine and imaging, Preschool, 030304 developmental biology, business.industry, Infant, medicine.disease, Lipid Metabolism, Musculoskeletal Abnormalities, Desmosterolosis, Radiography, Endocrinology, Pediatrics, Perinatology and Child Health, business, Epiphyseal stippling
Abstract

International audience; Disorders of post-squalene cholesterol biosynthesis are inborn errors of metabolism characterised by multiple congenital abnormalities, including significant skeletal involvement. The most frequent and best-characterised example is the Smith-Lemli-Opitz syndrome. Nine other disorders are known, namely autosomal-recessive Antley-Bixler syndrome, Greenberg dysplasia, X-linked dominant chondrodysplasia punctata, X-linked recessive male emopamil-binding protein deficiency, CHILD syndrome, CK syndrome, sterol C4 methyloxidase-like deficiency, desmosterolosis and lathosterolosis. This study provides an overview of the radiologic features observed in these diseases. A common pattern of limb abnormalities is recognisable, including polydactyly, which is typically post-axial and rarely interdigital and can involve all four limbs, and syndactyly of the toes. Chondrodysplasia punctata is specifically associated with a subgroup of disorders of cholesterol biosynthesis (Greenberg dysplasia, CHILD syndrome, X-linked dominant chondrodysplasia punctata, male emopamil-binding protein deficiency). The possible occurrence of epiphyseal stippling in the Smith-Lemli-Opitz syndrome, initially reported, does not appear to be confirmed. Stippling is also associated with other congenital disorders such as chromosomal abnormalities, brachytelephalangic chondrodysplasia punctata (X-linked recessive chondrodysplasia punctata, disruptions of vitamin K metabolism, maternal autoimmune diseases), rhizomelic chondrodysplasia punctata (peroxisomal disorders) and lysosomal storage disorders. In the differential diagnosis of epiphyseal stippling, a moth-eaten appearance of bones, asymmetry, or presence of a common pattern of limb abnormalities indicate inborn errors of cholesterol biosynthesis. We highlight the specific differentiating radiologic features of disorders of post-squalene cholesterol biosynthesis.

Published
2015

264. Refinement of Genotype-Phenotype Correlation in 18 Patients Carrying a 1q24q25 Deletion

Author

Caroline Schluth-Bolard, Claudia A. L. Ruivenkamp, Brigitte Benzacken, Zeynep Tümer, Joris Andrieux, Nicole Bain, Kerry Fagan, Nicolas Chatron, Marianne Till, Damien Sanlaville, Clarisse Baumann, Odile Boute, P. Edery, Laura Bernardini, Céline Bonnet, Anna Hackett, Massimiliano Rossi, Bruno Leheup, Julie Désir, Arie van Haeringen, Séverine Drunat, Yves Alembik, Véronique Haddad, Marion Gérard, Pia Castelluccio, Anne Dieux, Helen Stewart, Azzedine Aboura, Elisabeth Flori, Laura Roos, Joanna McParland, Laboratoire de Cytogénétique Constitutionnelle [Hospices civils de Lyon], Hospices Civils de Lyon (HCL), Unité de Cytogénétique [CHU Debré], AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Génétique Médicale, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut de Pathologie et Génétique [Gosselies] (I.P.G.), Service de Génétique clinique, Unité de Génétique Clinique [CHU Debré], Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de génétique [Hôpial Louis Pradel - HCL], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Cytogénétique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Génétique Clinique [Hautepierre Strasbourg], Hôpital de Hautepierre [Strasbourg], Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Mendel Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Ospedale Cardarelli, Department of Clinical Genetics [Copenhagen], Rigshospitalet [Copenhagen], Copenhagen University Hospital-Copenhagen University Hospital, University of Newcastle [Australia] (UoN), Department of Clinical Genetics, Leiden University Medical Centre, Clinical Cytogeneticist Laboratory for Diagnostic Genome Analysis [Leiden University Medical Center], Leiden University Medical Center (LUMC), Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-IFR2-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Cytogénétiqué, Hôpital Jean-Verdier, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University of Newcastle [Callaghan, Australia] (UoN), Universiteit Leiden-Universiteit Leiden, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Microcephaly, Pathology, medicine.medical_specialty, Microarray, Adolescent, [SDV]Life Sciences [q-bio], growth retardation, Biology, Single transverse palmar crease, Genetics, medicine, Humans, 1q24q25 deletion, Sex organ, Abnormalities, Multiple, 10. No inequality, Child, Genetics (clinical), Genetic Association Studies, In Situ Hybridization, Fluorescence, Aged, Comparative Genomic Hybridization, Brachydactyly, Infant, Newborn, brachydactyly, Chromosome, Infant, Middle Aged, DNM3, medicine.disease, Phenotype, Chromosomes, Human, Pair 1, intellectual disability, Child, Preschool, Female, medicine.symptom, Chromosome Deletion
Abstract

International audience; Interstitial deletion 1q24q25 is a rare rearrangement associated with intellectual disability, growth retardation, abnormal extremities and facial dysmorphism. In this study, we describe the largest series reported to date, including 18 patients (4M/14F) aged from 2 days to 67 years and comprising two familial cases. The patients presented with a characteristic phenotype including mild to moderate intellectual disability (100%), intrauterine (92%) and postnatal (94%) growth retardation, microcephaly (77%), short hands and feet (83%), brachydactyly (70%), fifth finger clinodactyly (78%) and facial dysmorphism with a bulbous nose (72%), abnormal ears (67%) and micrognathia (56%). Other findings were abnormal palate (50%), single transverse palmar crease (53%), renal (38%), cardiac (38%), and genital (23%) malformations. The deletions were characterized by chromosome microarray. They were of different sizes (490 kb to 20.95 Mb) localized within chromosome bands 1q23.3-q31.2 (chr1:160797550-192912120, hg19). The 490 kb deletion is the smallest deletion reported to date associated with this phenotype. We delineated three regions that may contribute to the phenotype: a proximal one (chr1:164,501,003-167,022,133), associated with cardiac and renal anomalies, a distal one (chr1:178,514,910-181,269,712) and an intermediate 490 kb region (chr1:171970575-172460683, hg19), deleted in the most of the patients, and containing DNM3, MIR3120 and MIR214 that may play an important role in the phenotype. However, this genetic region seems complex with multiple regions giving rise to the same phenotype.

Published
2015

265. Three-Dimensional Phenomena in Microbubble Acoustic Streaming

Author

Cheng Wang, Alvaro Marin, Bhargav Rallabandi, Massimiliano Rossi, Christian J. Kähler, and Sascha Hilgenfeldt

Subjects
Physics, Microfluidics, General Physics and Astronomy, Mechanics, Physics::Fluid Dynamics, symbols.namesake, Acoustic streaming, Character (mathematics), Flow (mathematics), Microfluidic channel, symbols, Streamlines, streaklines, and pathlines, Einstein, Micro bubble
Abstract

Flows in microfluidic channels are often assumed to be two-dimensional (2D). However, the authors find that the vortical structures of micro bubbles subject to vertically uniform acoustic agitation produce complex 3D trajectories, rather than the 2D streamlines that one would expect. As with Einstein's observations of 3D trajectories of swirling tea leaves in a cup, the 3D character of the flow can be traced to boundary effects. These results have important consequences for the behaviors of confined vortical microfluidic structures.

Published
2015

266. Baraitser-Winter cerebrofrontofacial syndrome : Delineation of the spectrum in 42 cases

Author

Sara Osimani, Andrew E. Fry, Koenraad Devriendt, Débora Romeo Bertola, Marjan M. Nezarati, Han G. Brunner, Grazia M.S. Mancini, Jorge L. Juncos, Pirayeh Eftekhari, Nataliya Di Donato, Marjolijn C.J. Jongmans, Laurence Faivre, Gilles Morin, Małgorzata J.M. Nowaczyk, Didier Lacombe, Zeichi-Seide Roseli, Conny M. A. van Ravenswaaij, Daniela Melis, Julien Masliah-Planchon, William B. Dobyns, Alexander Hoischen, Hatice Koçak Eker, Marlies Kempers, Andreas Rump, Vera Uliana, Victoria Mok Siu, Fabienne Giuliano, Nicole Philip, Beate Albrecht, Omar A Abdul-Raman, Alain Verloes, Mirjam Klaus, Angela E. Lin, Massimiliano Rossi, Albert David, Bregje W.M. van Bon, Jeanette C. Ramer, Ludivine Templin, Séverine Drunat, Yves Sznajer, Vincent Procaccio, Jean-Baptiste Rivière, Mary Ella M Pierpont, Francesca Faravelli, Judith Allanson, Leina Guion Almeida, Daniela T. Pilz, Cristina Rusu, Nicolas Chassaing, Charles Marques Lourenço, Bruce H. Wainer, Valérie Drouin-Garraud, Hôpital Robert Debré, Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Universitätsklinikum Carl Gustav Carus, Université Paris Diderot - Paris 7 (UPD7), Radboud University Medical Centre [Nijmegen, The Netherlands], University of Mississippi Medical Center (UMMC), Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen), Children's Hospital of Eastern Ontario [Ottawa, Canada], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre hospitalier universitaire de Nantes (CHU Nantes), University Hospital Gasthuisberg, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Rouen, Normandie Université (NU), Ospedale Galliera, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Nice (CHU Nice), University of São Paulo (USP), Emory University School of Medicine, Emory University [Atlanta, GA], CHU Bordeaux [Bordeaux], Massachusetts General Hospital [Boston], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Università degli studi di Napoli Federico II, University of Western Ontario (UWO), CHU Amiens-Picardie, McMaster University [Hamilton, Ontario], Pennsylvania State University (Penn State), Penn State System, Hôpital de la Timone [CHU - APHM] (TIMONE), University of Minnesota [MN, USA], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Cliniques Universitaires Saint-Luc [Bruxelles], University Hospital Groningen, University Hospital of Wales [Cardiff, UK], Seattle Children’s Hospital, Clinical Genetics, UCL - SSS/IREC - Institut de recherche expérimentale et clinique, UCL - (SLuc) Centre de génétique médicale UCL, Ethical, Legal, Social Issues in Genetics (ELSI), and Clinical Cognitive Neuropsychiatry Research Program (CCNP)

Subjects
Male, Microcephaly, Pathology, Craniofacial abnormality, [SDV]Life Sciences [q-bio], Medizin, GYRAL MALFORMATIONS, Craniofacial Abnormalities, FUNCTIONAL DIVERSITY, 0302 clinical medicine, Ptosis, Gene Order, Genetics(clinical), Hypertelorism, Non-U.S. Gov't, Child, Genetics (clinical), Arthrogryposis, Dystonia, 0303 health sciences, Research Support, Non-U.S. Gov't, Anatomy, 3. Good health, Phenotype, Child, Preschool, Female, medicine.symptom, Abnormalities, Multiple, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], Adult, medicine.medical_specialty, APPARENTLY UNDESCRIBED SYNDROME, Adolescent, Lissencephaly, Biology, Research Support, Article, 03 medical and health sciences, Young Adult, SDG 3 - Good Health and Well-being, medicine, Genetics, Journal Article, Humans, Abnormalities, Multiple, Preschool, 030304 developmental biology, SHALLOW ORBITS, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], GAMMA-ACTIN, Pachygyria, Facies, medicine.disease, IRIS COLOBOMA, Actins, BETA-ACTIN, Amino Acid Substitution, Genetic Loci, Mutation, FACIAL SYNDROME, 030217 neurology & neurosurgery, MENTAL-RETARDATION, GROWTH-RETARDATION
Abstract

International audience; Baraitser-Winter, Fryns-Aftimos and cerebrofrontofacial syndrome types 1 and 3 have recently been associated with heterozygous gain-of-function mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1 that encode beta- and gamma-actins. We present detailed phenotypic descriptions and neuroimaging on 36 patients analyzed by our group and six cases from the literature with a molecularly proven actinopathy (9 ACTG1 and 33 ACTB). The major clinical anomalies are striking dysmorphic facial features with hypertelorism, broad nose with large tip and prominent root, congenital non-myopathic ptosis, ridged metopic suture and arched eyebrows. Iris or retinal coloboma is present in many cases, as is sensorineural deafness. Cleft lip and palate, hallux duplex, congenital heart defects and renal tract anomalies are seen in some cases. Microcephaly may develop with time. Nearly all patients with ACTG1 mutations, and around 60% of those with ACTB mutations have some degree of pachygyria with anteroposterior severity gradient, rarely lissencephaly or neuronal heterotopia. Reduction of shoulder girdle muscle bulk and progressive joint stiffness is common. Early muscular involvement, occasionally with congenital arthrogryposis, may be present. Progressive, severe dystonia was seen in one family. Intellectual disability and epilepsy are variable in severity and largely correlate with CNS anomalies. One patient developed acute lymphocytic leukemia, and another a cutaneous lymphoma, indicating that actinopathies may be cancer-predisposing disorders. Considering the multifaceted role of actins in cell physiology, we hypothesize that some clinical manifestations may be partially mutation specific. Baraitser-Winter cerebrofrontofacial syndrome is our suggested designation for this clinical entity.European Journal of Human Genetics advance online publication, 23 July 2014; doi:10.1038/ejhg.2014.95.

Published
2015

267. Perspectives actuelles dans la microdélétion 22q11.2 : prise en charge du phénotype neurocomportemental

Author

Thierry d'Amato, Stephan Eliez, Patrick Edery, Nicolas Franck, Massimiliano Rossi, Caroline Demily, Arnaud Leleu, Maude Schneider, Centre de dépistage et de prise en charge des troubles psychiatriques d’origine génétique, pôle Ouest, Centre Hospitalier le Vinatier [Bron], Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Université de Genève (UNIGE), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université de Bourgogne (UB), Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 ( CNC ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Hospices Civils de Lyon ( HCL ), Université de Genève ( UNIGE ), Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Université de Bourgogne ( UB ), and Centre National de la Recherche Scientifique ( CNRS )

Subjects
medicine.medical_specialty, cognition sociale, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, neurocognition, social cognition, anomalies cytogénétiques, psychose, Arts and Humanities (miscellaneous), remédiation cognitive, adhd, Medicine, psychosis, Gynecology, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, syndrome de digeorge, 3. Good health, schizophrenia, Psychiatry and Mental health, chromosomal abnormalities, schizophrénie, 22q11.2 deletion syndrome, [ SCCO.NEUR ] Cognitive science/Neuroscience, cognitive remediation, business, digeorge's syndrome, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Resume La microdeletion 22q11.2 est le syndrome microdeletionnel le plus frequent de la population generale. Le phenotype associe des anomalies de l’appareil pharynge embryonnaire a un phenotype neurocomportemental. La presentation clinique du syndrome est extremement variable d’un individu a l’autre, quelle que soit la taille de la deletion, et plus de 180 manifestations ont ete decrites, aucune n’etant pathognomonique. Les symptomes psychiatriques, particulierement de nature psychotique, sont frequents dans la microdeletion 22q11.2 et de nombreux psychiatres sont amenes a rencontrer ces patients. La prise en charge doit tenir compte des particularites du syndrome. L’evaluation de la neurocognition, de la cognition sociale et la recherche de symptomes psychiatriques dans le contexte medical general sont une etape fondamentale. Concernant le phenotype neurocomportemental, les soins de remediation cognitive doivent etre combines a une prescription mesuree de psychotropes pour aboutir a une meilleure qualite de vie de ces patients.

Published
2015

268. Astigmatic Micro Particle Imaging

Author

Massimiliano Rossi, Christian Cierpka, and Christian J. Kähler

Subjects
Physics, business.industry, Microfluidics, Measure (physics), Micromixer, Astigmatism, medicine.disease, Optics, Position (vector), Measuring principle, TRACER, medicine, business, Mixing (physics)
Abstract

Astigmatism particle imaging is an optical method to determine the instantaneous volumetric position of spherical particles in a volume of transparent medium using only a single camera view. The method is mainly applied in microfluidics to measure the velocity and trajectories of tracer particles that follow the fluid motion. However, recently it could be shown that this measurement principle without bias errors due to the depth of correlation and spatial averaging is well suited to reconstruct the arbitrary-shaped interface of mixing layers in a micromixer with extended high precision.

Published
2015

269. New insights into genotype-phenotype correlation for GLI3 mutations

Author

Florence Demurger, Amanda Krause, Tania Attié-Bitach, Muriel Holder, Clarisse Baumann, Mélanie Fradin, Alain Liquier, Joelle Roume, Laurent Pasquier, Fabienne Giuliano, Valérie Cormier-Daire, Daniel Amram, Martine Le Merrer, Odile Boute, Chloé Quélin, Férechté Encha-Razavi, Serge Romana, Marie-Liesse Chauvet, Soumaya Mougou-Zerelli, Lionel Van Maldergem, Bertrand Isidor, Sylvie Odent, Fanny Laffargue, Massimiliano Rossi, Sylvie Manouvrier, Marie-Ange Delrue, Sheela Nampoothiri, André Mégarbané, Marie Gonzales, Alexandra Afenjar, Louise Devisme, Gwenaelle André, Martine Sinico, Anne Dieux-Coeslier, Nicole Philip, Sandra Mercier, Odile Raoul, Géraldine Viot, Marie-Line Jacquemont, Elise Schaefer, Laurence Faivre, Géraldine Goudefroye, Didier Lacombe, Amale Ichkou, Michel Vekemans, Marylin Lackmy-Port-Lis, Arnold Munnich, Jeanne Amiel, Anne-Lise Delezoide, Catherine Vincent-Delorme, Geneviève Baujat, David Geneviève, Service de Cytogénétique et de Biologie Cellulaire, Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cytogénétique, Génétique moléculaire et Biologie de la reproduction, Hôpital Farhat Hached, Service de Biologie du Développement, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), PremUp Foundation, Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-CHI Créteil-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Génétique, Hôpital de Hautepierre [Strasbourg], Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de génétique clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Amrita Institute of Medical Sciences and Research Center, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Poissy-saint Germain, Service de Génétique Médicale, Centre hospitalier universitaire de Nantes (CHU Nantes), Maladies Rares - Génétique et Métabolisme (MRGM), Université Bordeaux Segalen - Bordeaux 2-Hôpital Pellegrin-Service de Génétique Médicale du CHU de Bordeaux, Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Référence ' Anomalies du Développement et Syndromes Malformatifs Sud - Est PACA ', Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Génétique clinique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Division of human Genetics, University of the Witwatersrand [Johannesburg] (WITS)-National Health Laboratory Service-School of Pathology, Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service d'AnatomoPathologie, CHI Créteil, Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, Service de génétique médicale, Hôpital l'Archet, Head of the Department of Medical Genetics, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Trousseau [APHP], Regional Hospital, Centre de Maladies Rares, Anomalies du Développement Nord de France-CH Arras - CHRU Lille, Pôle de Pathologie, Centre de Biologie Pathologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cellules souches mésenchymateuses, environnement articulaire et immunothérapies de la polyarthrite rhumatoide, Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Service de Génétique [Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], INSERM EMI0210 (EMI0210), Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Histologie Embryologie Cytogénétique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Service de Cytogénétique et Embryologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de Génétique Clinique, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-hôpital Sud, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Descartes - Paris 5 (UPD5)-CHI Créteil-Institut de Recherche pour le Développement (IRD)-Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Centre National de la Recherche Scientifique (CNRS), Unité Fonctionnelle de Génétique Clinique [CHU Pitié Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de génétique et embryologie médicales [CHU Trousseau], Jonchère, Laurent, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Sud, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Universités-Université Paris Descartes - Paris 5 ( UPD5 ) -CHI Créteil-Institut de Recherche pour le Développement ( IRD ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -CHU Pontchaillou [Rennes]-Hôpital Sud, Service de Génétique Clinique et Université Lille 2, Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Centre National de la Recherche Scientifique ( CNRS ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, CHU Cochin [AP-HP], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Maladies Rares - Génétique et Métabolisme ( MRGM ), Génétique Médicale et Génomique Fonctionnelle ( GMGF ), Aix Marseille Université ( AMU ) -Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), University of the Witwatersrand [Johannesburg] ( WITS ) -National Health Laboratory Service-School of Pathology, Service de Génétique Médical, CHU Clermont-Ferrand, Hospices Civils de Lyon ( HCL ) -CHU de Lyon-Centre Neuroscience et Recherche, Unité Fonctionnelle de Génétique Clinique, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]-Centre de référence 'Déficiences Intellectuelles de Causes Rares' - Paris-Groupe de Recherche Clinique 'Déficience Intellectuelle et Autisme' - Paris, Service de Neuropédiatrie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], INSERM EMI0210 ( EMI0210 ), and Institut National de la Santé et de la Recherche Médicale ( INSERM )

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, animal structures, Agnathia, Acrocephalosyndactylia, DNA Mutational Analysis, Kruppel-Like Transcription Factors, Gene Expression, Nerve Tissue Proteins, Haploinsufficiency, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, Article, Cohort Studies, 03 medical and health sciences, Zinc Finger Protein Gli3, GLI3, Genetics, medicine, Humans, Abnormalities, Multiple, Family, Genetic Association Studies, In Situ Hybridization, Fluorescence, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Gene Rearrangement, Greig cephalopolysyndactyly syndrome, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, 030305 genetics & heredity, Gene rearrangement, medicine.disease, Phenotype, 3. Good health, body regions, Polysyndactyly, Mutation, embryonic structures, [ SDV.GEN ] Life Sciences [q-bio]/Genetics
Abstract

International audience; The phenotypic spectrum of GLI3 mutations includes autosomal dominant Greig cephalopolysyndactyly syndrome (GCPS) and Pallister-Hall syndrome (PHS). PHS was first described as a lethal condition associating hypothalamic hamartoma, postaxial or central polydactyly, anal atresia and bifid epiglottis. Typical GCPS combines polysyndactyly of hands and feet and craniofacial features. Genotype-phenotype correlations have been found both for the location and the nature of GLI3 mutations, highlighting the bifunctional nature of GLI3 during development. Here we report on the molecular and clinical study of 76 cases from 55 families with either a GLI3 mutation (49 GCPS and 21 PHS), or a large deletion encompassing the GLI3 gene (6 GCPS cases). Most of mutations are novel and consistent with the previously reported genotype-phenotype correlation. Our results also show a correlation between the location of the mutation and abnormal corpus callosum observed in some patients with GCPS. Fetal PHS observations emphasize on the possible lethality of GLI3 mutations and extend the phenotypic spectrum of malformations such as agnathia and reductional limbs defects. GLI3 expression studied by in situ hybridization during human development confirms its early expression in target tissues.European Journal of Human Genetics advance online publication, 16 April 2014; doi:10.1038/ejhg.2014.62.

Published
2015

270. Intragenic KANSL1 mutations and chromosome 17q21.31 deletions: broadening the clinical spectrum and genotype-phenotype correlations in a large cohort of patients

Author

Domenica Battaglia, Roseline Caumes, Matteo Della Monica, Giuseppe Marangi, Marni J. Falk, Manuela Priolo, Patrick Edery, Maria Chiara Stefanini, Emanuela Ponzi, Beatrice Oneda, Daniela Orteschi, Raymon Vijzelaar, Holly Dubbs, Sulagna C. Saitta, Matthew A. Deardorff, Serena Lattante, Marcella Zollino, Mattia Gentile, Francesca Scarano, Massimiliano Rossi, Maria Piccione, Omar A. Abdul-Rahman, Eugenio Mercuri, Marina Murdolo, Ilaria Contaldo, Giuseppe Zampino, Stefania Ricciardi, Anita Rauch, Elaine H. Zackai, Giovanni Corsello, Zollino, M., Marangi, G., Ponzi, E., Orteschi, D., Ricciardi, S., Lattante, S., Murdolo, M., Battaglia, D., Contaldo, I., Mercuri, E., Stefanini, M., Caumes, R., Edery, P., Rossi, M., Piccione, M., Corsello, G., Della Monica, M., Scarano, F., Priolo, M., Gentile, M., Zampino, G., Vijzelaar, R., Abdulrahman, O., Rauch, A., Oneda, B., Deardorff, M., Saitta, S., Falk, M., Dubbs, H., and Zackai, E.

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, genotype-phenotype correlations, Koolen De Vries syndrome, KANSL1 mutation, Haploinsufficiency, Biology, Settore MED/03 - GENETICA MEDICA, Severity of Illness Index, Craniofacial Abnormalities, Young Adult, Seizures, Molecular genetics, Genetics, medicine, Humans, Abnormalities, Multiple, Language Development Disorders, Child, Genetics (clinical), Genetic Association Studies, Optic nerve hypoplasia, Fetal Growth Retardation, Point mutation, Macrocephaly, Infant, Nuclear Proteins, Syndrome, clinical heterogeneity, Smith–Magenis syndrome, medicine.disease, Child, Preschool, Speech delay, Female, medicine.symptom, Chromosome Deletion, Smith-Magenis Syndrome, Chromosomes, Human, Pair 17, 17q21.31 deletion
Abstract

Background The 17q21.31 deletion syndrome phenotype can be caused by either chromosome deletions or point mutations in the KANSL1 gene. To date, about 60 subjects with chromosome deletion and 4 subjects with point mutation in KANSL1 have been reported. Prevalence of chromosome deletions compared with point mutations, genotype–phenotype correlations and phenotypic variability have yet to be fully clarified. Methods We report genotype–phenotype correlations in 27 novel subjects with 17q21.31 deletion and in 5 subjects with KANSL1 point mutation , 3 of whom were not previously reported. Results The prevalence of chromosome deletion and KANSL1 mutation was 83% and 17%, respectively. All patients had similar clinical features, with the exception of macrocephaly, which was detected in 24% of patients with the deletion and 60% of those with the point mutation, and congenital heart disease, which was limited to 35% of patients with the deletion. A remarkable phenotypic variability was observed in both categories, mainly with respect to the severity of ID. Cognitive function was within normal parameters in one patient in each group. Craniosynostosis, subependymal heterotopia and optic nerve hypoplasia represent new component manifestations. Conclusions In KANSL1 haploinsufficiency syndrome, chromosome deletions are greatly prevalent compared with KANSL1 mutations. The latter are sufficient in causing the full clinical phenotype. The degree of intellectual disability (ID) appears to be milder than expected in a considerable number of subjects with either chromosome deletion or KANSL1 mutation. Striking clinical criteria for enrolling patients into KANSL1 analysis include speech delay, distinctive facial dysmorphism, macrocephaly and friendly behaviour.

Published
2015

272. Complex phenotype with social communication disorder caused by mosaic supernumerary ring chromosome 19p

Author

Alice Poisson, Caroline Demily, Brice Martin, Patrick Edery, Massimiliano Rossi, Gabrielle Chesnoy-Servanin, and Damien Sanlaville

Subjects
Adult, Male, medicine.medical_specialty, Duplication, Autism, Neurodevelopment, Ring chromosome, Case Report, Trisomy, Biology, Chromosome 19, Genetics, medicine, Humans, Ring Chromosomes, Genetics(clinical), Copy-number variation, Genetics (clinical), Copy number variants, medicine.diagnostic_test, Chromosomal abnormalities, Mosaicism, Cytogenetics, medicine.disease, Human genetics, Social communication disorder, Phenotype, Communication Disorders, Chromosomes, Human, Pair 19, Fluorescence in situ hybridization, Comparative genomic hybridization
Abstract

Background Deletions or duplications of chromosome 19 are rare and there is no previous report in the literature of a ring chromosome derived from proximal 19p. Copy Number Variants (CNVs) responsible for complex phenotypes with Social Communication Disorder (SCD), may contribute to improve knowledge about the distinction between intellectual deficiency and autism spectrum disorders. Case presentation We report the clinical and cytogenetic characterization of a patient (male, 33 years-old, first child of healthy Portuguese non-consanguineous parents) presenting with a complex phenotype including SCD without intellectual deficiency and carrying a mosaic supernumerary ring chromosome 19p. Microarray-Based Comparative Genomic Hybridization and Fluorescence in situ Hybridization were performed. Genetic analysis showed a large mosaic interstitial duplication 19p13.12p12 of the short arm of chromosome 19, spanning 8.35 Mb. Our data suggested a putative association between psychosocial dysfunction and mosaic pure trisomy 19p13.2p12. Conclusion This clinical report demonstrated the need to analyze more discreet trait-based subsets of complex phenotypes to improve the ability to detect genetic effects. To address this question and the broader issue of deciphering the yet unknown genetic contributors to complex phenotype with SCD, we suggest performing systematic psychological and psychiatric assessments in patients with chromosomal abnormalities.

Published
2014

273. A new familial case of spondylo-epi-metaphyseal dysplasia with multiple dislocations Hall type (leptodactylic form)

Author

Gianfranco Sebastio, Daniele De Brasi, Antonella Battagliese, Generoso Andria, Daniela Melis, Christine Hall, Massimiliano Rossi, Rossi, M, DE BRASI, Daniele, Hall, Cm, Battagliese, A, Melis, Daniela, Sebastio, Gianfranco, and Andria, Generoso

Subjects
Adult, Male, Hand deformity, Foot Deformities, Congenital, business.industry, Spondylo epi metaphyseal dysplasia, Body height, Infant, General Medicine, Anatomy, Osteochondrodysplasias, medicine.disease, Body Height, Pathology and Forensic Medicine, MULTIPLE DISLOCATIONS, Familial case, Dysplasia, Pediatrics, Perinatology and Child Health, Humans, Medicine, business, Hand Deformities, Congenital, Genetics (clinical)
Abstract

We report a father and son affected by spondylo-epi-metaphyseal dysplasia with multiple dislocations (Hall type), also called leptodactylic form. This family contributes to the delineation of the clinical and radiological phenotype of this rare condition.

Published
2005

274. Maternal apo E genotype is a modifier of the Smith-Lemli-Opitz syndrome

Author

Massimiliano Rossi, M Giros, M Gruber, M Krajewska-Walasek, Gerd Utermann, Peter E. Clayton, Dorothea Haas, H. G. Kraft, Martina Witsch-Baumgartner, and Richard I. Kelley

Subjects
Male, Apolipoprotein E, Oxidoreductases Acting on CH-CH Group Donors, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Genotype, macromolecular substances, Biology, Polymorphism, Single Nucleotide, Severity of Illness Index, Apolipoproteins E, chemistry.chemical_compound, Gene Frequency, Internal medicine, Genetics, medicine, Humans, Allele, Allele frequency, Alleles, Genetics (clinical), Analysis of Variance, Cholesterol, Membrane Proteins, medicine.disease, Protein Structure, Tertiary, Smith-Lemli-Opitz Syndrome, Hypocholesterolemia, Logistic Models, Phenotype, Endocrinology, Receptors, LDL, chemistry, Smith–Lemli–Opitz syndrome, Face, Regression Analysis, Original Article, Female, lipids (amino acids, peptides, and proteins), Peptides
Abstract

BACKGROUND: Smith-Lemli-Opitz syndrome (MIM 270400) is an autosomal recessive malformation and mental retardation syndrome that ranges in clinical severity from minimal dysmorphism and mild mental retardation to severe congenital anomalies and intrauterine death. Smith-Lemli-Opitz syndrome is caused by mutations in the Delta7 sterol-reductase gene (DHCR7; EC 1.3.1.21), which impair endogenous cholesterol biosynthesis and make the growing embryo dependent on exogenous (maternal) sources of cholesterol. We have investigated whether apolipoprotein E, a major component of the cholesterol transport system in human beings, is a modifier of the clinical severity of Smith-Lemli-Opitz syndrome. METHOD: Common apo E, DHCR7, and LDLR genotypes were determined in 137 biochemically characterised patients with Smith-Lemli-Opitz syndrome and 59 of their parents. RESULTS: There was a significant correlation between patients' clinical severity scores and maternal apo E genotypes (p = 0.028) but not between severity scores and patients' or paternal apo E genotypes. In line with their effects on serum cholesterol levels, the maternal apo epsilon2 genotypes were associated with a severe Smith-Lemli-Opitz syndrome phenotype, whereas apo E genotypes without the epsilon2 allele were associated with a milder phenotype. The correlation of maternal apo E genotype with disease severity persisted after stratification for DHCR7 genotype. There was no association of Smith-Lemli-Opitz syndrome severity with LDLR gene variation. CONCLUSIONS: These results suggest that the efficiency of cholesterol transport from the mother to the embryo is affected by the maternal apo E genotype and extend the role of apo E and its disease associations to modulation of embryonic development and malformations.

Published
2004

275. Femtosecond dynamics of Co thin films on Si support

Author

Fulvio Parmigiani, Gian Piero Banfi, Massimiliano Rossi, Alberto Comin, and Cristina Mozzati

Subjects
Kerr effect, Condensed matter physics, Magnetometer, Chemistry, Physics::Optics, General Chemistry, Condensed Matter Physics, Magnetic hysteresis, law.invention, Magnetization, Hysteresis, Magneto-optic Kerr effect, law, Picosecond, Femtosecond, Materials Chemistry
Abstract

The ultrafast electron and spin dynamics of Co films was investigated using a femto-second pump-probe technique. The samples were magnetically characterized by means of magnetooptical Kerr effect and non-optical magnetometers, i.e. superconductive quantum interference device and alternating gradient field magnetometer. Time evolution of both, Kerr rotation and ellipticity, was measured at different points of the static hysteresis cycle. This allowed separating magnetic and non-magnetic contributions to the signal. The sample magnetization was found to drop within 200 fs, following the pulse cross-correlation trace, while the magnetization recovery time was found to last few picoseconds.

Published
2004

276. Unbalanced translocation (3;5)(q26.1;p14): A clinical report

Author

Lucia Perone, Vito Guzzetta, Emilia Iaccarino, Generoso Andria, Maria Vittoria Andreucci, Maria Grazia Marzano, Daniele De Brasi, Pasqua Di Micco, Massimiliano Rossi, Giovanna Roberta Vega, Rossi, M, Di Micco, P, Perone, L, De Brasi, D, Guzzetta, V, Andreucci, Mv, Vega, Gr, Marzano, Mg, Iaccarino, E, and Andria, Generoso

Subjects
Male, congenital, hereditary, and neonatal diseases and abnormalities, Monosomy, medicine.medical_specialty, Pathology, Chromosomal translocation, Biology, Translocation, Genetic, Diagnosis, Differential, Fatal Outcome, Intellectual Disability, Internal medicine, Gene duplication, medicine, Humans, Abnormalities, Multiple, translocation (3,5)(q26.1,p14), Genetics (clinical), Infant, Karyotype, medicine.disease, Smith-Lemli-Opitz Syndrome, Endocrinology, Smith–Lemli–Opitz syndrome, Child, Preschool, Karyotyping, dup, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 3, Differential diagnosis, Trisomy
Abstract

A patient with a multiple congenital anomalies/mental retardation (MCA/MR) syndrome had an unbalanced translocation (3;5)(q26.1;p14), causing partial 5p monosomy and partial 3q trisomy. The phenotype observed in this patient results from the combination of those described in the isolated dup(3q) and del(5p) syndromes. Some clinical features of this patient are shared by the Smith-Lemli-Opitz syndrome (SLOS), a well-known MCA/MR syndrome due to the deficiency of 7-dehydrocholesterol reductase (DHCR7). We review the previously reported cases of chromosomal anomalies with clinical features suggesting SLOS.

Published
2002

277. Evaluation of long-term efficacy and tolerability of irbesartan in elderly hypertensive patients with renal impairment in an open-label study

Author

Piercarmine Cardace, Maria Leonarda De Rosa, Alessandro De Cristofaro, Massimiliano Rossi, and Antonio Baiano

Subjects
Pharmacology, medicine.medical_specialty, education.field_of_study, Hyperkalemia, business.industry, Population, Urology, Renal function, Effective renal plasma flow, urologic and male genital diseases, medicine.disease, Irbesartan, Blood pressure, Endocrinology, Tolerability, Internal medicine, medicine, Pharmacology (medical), Myocardial infarction, medicine.symptom, business, education, medicine.drug
Abstract

Background: Hypertension, left untreated, can lead to serious complications, including stroke myocardial infarction, and renal failure. Because lowering blood pressure correlates with slowing of renal disease progression, the control of hypertension in the presence of renal disease is essential. Objective: We evaluated the efficacy, tolerability, and safety of irbesartan alone or in combination with other antihypertensive agents in elderly patients with hypertension and chronic renal insufficiency. Methods: Patients > 65 years of age with hypertension (sitting diastolic blood pressure [SiDBP] 90–115 mm Hg) and chronic renal sufficiency that was mild (creatinine clearance [CrCL] 30–60 mL/min per 1.73 m 2 ) or moderate to severe CrCL 10–29 mL/min per 1.73 m 2 ) were enrolled. After a 3-week placebo run-in period, irbesartan was administered for 12 months at 150 mg/d. After 4 weeks of therapy, patients whose blood pressure was not adequately controlled (ie, SiDBP ≥90 mm Hg or p -aminohippurate were performed in a subset of patients. Results: A total of 32 patients (21 men, 11 women; mean age, 70.4 years) were enrolled. Thirty patients had mild renal insufficiency (mean CrCL, 44.45 mL/min per 1.73 m 2 ) and 2 patients had moderate to severe renal insufficiency (mean CrCL 21.32 mL/min per 1.73 m 2 ). Trough sitting blood pressures were reduced at the end of the first week of treatment in all groups. After 8 weeks, 12 weeks, and 1 year of treatment, the mean reductions in systolic blood pressure (SBP)/DBP were −11.9/−8.7 mm Hg, −10.8/−9.4 mm Hg, and −14.7/−12.1 mm Hg, respectively, in patients with mild renal insufficiency and −7.7/−6.3 mm Hg, −13.1/−11.8 mm Hg, and −14.1/−10.6 mm Hg in patients with moderate to severe renal insufficiency. CrCL, glomerular filtration rate, and effective renal plasma flow, as measured in a subset of 11 patients, were stable. Treatment was discontinued for 3 patients because of a clinical adverse event or laboratory parameter abnormality. Hyperkalemia (>6 mEq/L) requiring discontinuation of irbesartan occurred in 1 patient with moderate to severe renal insufficiency. Conclusion: The results of this study suggest that irbesartan, as monotherapy (150 mg once daily) or in combination with other antihypertensive drugs, is effective in reducing blood pressure in elderly hypertensive patients with chronic renal impairment and that irbesartan regimens are well tolerated in this population.

Published
2002

278. Next-generation sequencing (NGS) is a powerful tool to improve diagnostic yield in intellectual disability

Author

Patrick Edery, V. des Portes, M. Till, Nicolas Chatron, Linda Pons, Gaetan Lesca, Audrey Labalme, Marie-Pierre Cordier, Massimiliano Rossi, Audrey Putoux, and Damien Sanlaville

Subjects
Computer science, Yield (finance), Pediatrics, Perinatology and Child Health, Intellectual disability, medicine, Neurology (clinical), General Medicine, Bioinformatics, medicine.disease, Data science, DNA sequencing
Published
2017

279. International Dispersal of Dengue through Air Travel: Importation Risk for Europe

Author

Massimiliano Rossi, Wei Hu, Jennifer Miniota, Jan C. Semenza, David Kossowsky, Wim Van Bortel, Jonathan E. Suk, Kamran Khan, and Bertrand Sudre

Subjects
Veterinary medicine, Spatial Epidemiology, Epidemiology, viruses, Distribution (economics), Plant Science, Disease Vectors, Disease Informatics, Disease Outbreaks, law.invention, Dengue fever, Dengue, Aedes, law, Medicine and Health Sciences, Travel medicine, Socioeconomics, General Environmental Science, biology, Ecology, lcsh:Public aspects of medicine, 3. Good health, Europe, Air Travel, Infectious Diseases, Transmission (mechanics), Geography, Female, Research Article, Risk, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, Aedes albopictus, lcsh:RC955-962, education, Disease Surveillance, Infectious Disease Epidemiology, medicine, Animals, Humans, Disease Dynamics, Air travel, business.industry, Public health, fungi, Public Health, Environmental and Occupational Health, Biology and Life Sciences, Outbreak, lcsh:RA1-1270, Dengue Virus, Plant Pathology, biology.organism_classification, medicine.disease, Insect Vectors, Vector (epidemiology), General Earth and Planetary Sciences, Biological dispersal, business
Abstract

Background The worldwide distribution of dengue is expanding, in part due to globalized traffic and trade. Aedes albopictus is a competent vector for dengue viruses (DENV) and is now established in numerous regions of Europe. Viremic travellers arriving in Europe from dengue-affected areas of the world can become catalysts of local outbreaks in Europe. Local dengue transmission in Europe is extremely rare, and the last outbreak occurred in 1927–28 in Greece. However, autochthonous transmission was reported from France in September 2010, and from Croatia between August and October 2010. Methodology We compiled data on areas affected by dengue in 2010 from web resources and surveillance reports, and collected national dengue importation data. We developed a hierarchical regression model to quantify the relationship between the number of reported dengue cases imported into Europe and the volume of airline travellers arriving from dengue-affected areas internationally. Principal Findings In 2010, over 5.8 million airline travellers entered Europe from dengue-affected areas worldwide, of which 703,396 arrived at 36 airports situated in areas where Ae. albopictus has been recorded. The adjusted incidence rate ratio for imported dengue into European countries was 1.09 (95% CI: 1.01–1.17) for every increase of 10,000 travellers; in August, September, and October the rate ratios were 1.70 (95%CI: 1.23–2.35), 1.46 (95%CI: 1.02–2.10), and 1.35 (95%CI: 1.01–1.81), respectively. Two Italian cities where the vector is present received over 50% of all travellers from dengue-affected areas, yet with the continuing vector expansion more cities will be implicated in the future. In fact, 38% more travellers arrived in 2013 into those parts of Europe where Ae. albopictus has recently been introduced, compared to 2010. Conclusions The highest risk of dengue importation in 2010 was restricted to three months and can be ranked according to arriving traveller volume from dengue-affected areas into cities where the vector is present. The presence of the vector is a necessary, but not sufficient, prerequisite for DENV onward transmission, which depends on a number of additional factors. However, our empirical model can provide spatio-temporal elements to public health interventions., Author Summary The global disease burden of dengue is staggering. Continuous expansion and vaccine failures illustrate the limitations of current dengue control efforts. Novel approaches and additional tools are required to combat and contain the disease. In Europe, dengue infections are rare and the last outbreak of dengue occurred in the late 1920s, in Greece. In 2010, however, local transmission occurred in France and Croatia. Based on 2010 data, we present a novel quantitative model of the risk of dengue importation for Europe. The 2010 model predicts the risk of dengue importation to be greatest for Milan, Rome and Barcelona in August, September and October, precisely when vector activity is the highest. With the current expansion of the vector in Europe, more cities are projected to be at risk in the future. Thus, the model based on 2010 data quantifies the likelihood and timing of importation. This approach employs global travel data to assess dengue importation risk in the EU and illustrates how quantitative models could tailor infectious disease control to certain regions and time periods.

Published
2014

280. Optimization of astigmatic particle tracking velocimeters

Author

Christian J. Kähler and Massimiliano Rossi

Subjects
Fluid Flow and Transfer Processes, business.industry, Computer science, Monte Carlo method, Computational Mechanics, General Physics and Astronomy, Velocimetry, Tracking (particle physics), Displacement (vector), Optics, Cardinal point, Mechanics of Materials, Measuring principle, Cylindrical lens, Image sensor, business
Abstract

Astigmatic particle tracking velocimetry (APTV) has been developed in the last years to measure the three-dimensional displacement of tracer particles using a single-camera view. The measurement principle relies on an astigmatic optical system that provides aberrated particle images with a characteristic elliptical shape univocally related to the corresponding particle depth position. Because of the precision of this method, this concept is well established for measuring and controlling the distance between a CD/DVD and the reading head. The optical arrangement of an APTV system essentially consists of a primary stigmatic optics (e.g., a microscope, or a camera objective) and an astigmatic optics, typically a cylindrical lens placed in front of the camera sensor. This paper focuses on the uncertainty of APTV in the depth direction. First, an approximated analytical model is derived and experimentally validated. From the model, a set of three non-dimensional parameters that are the most significant in the optimization of the APTV performance are identified. Finally, the effect of different parameter settings and calibration approaches are studied systematically using numerical Monte Carlo simulations. The results allow for the derivation of general criteria to minimize the overall error in APTV measurements and provide the basis for reliable uncertainty estimation for a wide range of applications.

Published
2014

281. Environmental predictors of West Nile fever risk in Europe

Author

Véronique Chevalier, Annie Desbrosse, Annelise Tran, Bertrand Sudre, Massimiliano Rossi, Jan C. Semenza, and Shlomit Paz

Subjects
Epidemiology, Business, Management and Accounting(all), L73 - Maladies des animaux, Facteur climatique, terre humide, Logistic regression, Risk Factors, Analyse du risque, Facteur de risque, Arbovirus, education.field_of_study, Surveillance, Incidence (epidemiology), Temperature, Facteur du milieu, Vegetation, Environmental exposure, West nile virus, Remote sensing, B10 - Géographie, Europe, Épidémiologie, Geography, L20 - Écologie animale, Modèle mathématique, Computer Science(all), General Computer Science, P40 - Météorologie et climatologie, Distribution géographique, Télédétection, Population, Risk maps, Normalized Difference Vegetation Index, Birds, Animals, Humans, Surveillance épidémiologique, education, Paysage, Cartographie, Research, Flavivirus, Migration animale, Public Health, Environmental and Occupational Health, Outbreak, Modèle de simulation, Environmental Exposure, Oiseau, Température, General Business, Management and Accounting, Confidence interval, West nile fever, Wetlands, Environmental determinants, Écologie animale, U30 - Méthodes de recherche, Forecasting, Demography
Abstract

Background West Nile virus (WNV) is a mosquito-borne pathogen of global public health importance. Transmission of WNV is determined by abiotic and biotic factors. The objective of this study was to examine environmental variables as predictors of WNV risk in Europe and neighboring countries, considering the anomalies of remotely sensed water and vegetation indices and of temperature at the locations of West Nile fever (WNF) outbreaks reported in humans between 2002 and 2013. Methods The status of infection by WNV in relationship to environmental and climatic risk factors was analyzed at the district level using logistic regression models. Temperature, remotely sensed Normalized Difference Vegetation Index (NDVI) and Modified Normalized Difference Water Index (MNDWI) anomalies, as well as population, birds’ migratory routes, and presence of wetlands were considered as explanatory variables. Results The anomalies of temperature in July, of MNDWI in early June, the presence of wetlands, the location under migratory routes, and the occurrence of a WNF outbreak the previous year were identified as risk factors. The best statistical model according to the Akaike Information Criterion was used to map WNF risk areas in 2012 and 2013. Model validations showed a good level of prediction: area under Receiver Operator Characteristic curve = 0.854 (95% Confidence Interval 0.850-0.856) for internal validation and 0.819 (95% Confidence Interval 0.814-0.823) (2012) and 0.853 (95% Confidence Interval 0.850-0.855) (2013) for external validations, respectively. Conclusions WNF incidence is increasing in Europe and WNV is expanding into new areas where it had never been observed before. Our model can be used to direct surveillance activities and public health interventions for the upcoming WNF season.

Published
2014

282. Molecular characterization of a cohort of 73 patients with infantile spasms syndrome

Author

Emilie Bourel-Ponchel, Nadia Boutry-Kryza, Clotilde Rivier, Fabienne Prieur, Sarra Dimassi, Audrey Labalme, Patrick Edery, Massimiliano Rossi, Anne-Lise Poulat, A. Delignières, Marianne Till, Gaetan Lesca, Alain Calender, Julitta de Bellescize, Vincent des Portes, Damien Sanlaville, Dorothée Ville, Anne-Gaëlle Le Moing, and Renaud Touraine

Subjects
Male, DNA Copy Number Variations, Genetic counseling, Nedd4 Ubiquitin Protein Ligases, Ubiquitin-Protein Ligases, CDKL5, Biology, Protein Serine-Threonine Kinases, Bioinformatics, Receptors, N-Methyl-D-Aspartate, EHMT1, Munc18 Proteins, Calmodulin, Genetics, medicine, STXBP1, Humans, KCNQ2 Potassium Channel, Copy-number variation, Child, Genetics (clinical), Adaptor Proteins, Signal Transducing, NAV1.2 Voltage-Gated Sodium Channel, Endosomal Sorting Complexes Required for Transport, MEF2 Transcription Factors, Infant, Newborn, General Medicine, Histone-Lysine N-Methyltransferase, Syndrome, medicine.disease, Hypsarrhythmia, Epileptic spasms, Targeted Mutation, Child, Preschool, Mutation, Female, medicine.symptom, Carrier Proteins, Guanylate Kinases, Spasms, Infantile
Abstract

Infantile Spasms syndrome (ISs) is a characterized by epileptic spasms occurring in clusters with an onset in the first year of life. West syndrome represents a subset of ISs that associates spasms in clusters, a hypsarrhythmia EEG pattern and a developmental arrest or regression. Aetiology of ISs is widely heterogeneous including many genetic causes. Many patients, however, remain without etiological diagnosis, which is critical for prognostic purpose and genetic counselling. In the present study, we performed genetic screening of 73 patients with different types of ISs by array-CGH and molecular analysis of 5 genes: CDKL5, STXBP1, KCNQ2, and GRIN2A, whose mutations cause different types of epileptic encephalopathies, including ISs, as well as MAGI2, which was suggested to be related to a subset of ISs. In total, we found a disease-causing mutation or CNV (Copy Number Variation) in 15% of the patients. These included 6 point mutations found in CDKL5 (n = 3) and STXBP1 (n = 3), 3 microdeletions (10 Mb in 2q24.3, 3.2 Mb in 5q14.3 including the region upstream to MEF2C, and 256 kb in 9q34 disrupting EHMT1), and 2 microduplications (671 kb in 2q24.3 encompassing SCN2A, and 11.93 Mb in Xq28). In addition, we discuss 3 CNVs as potential risk factors, including one 16p12.1 deletion, one intronic deletion of the NEDD4 gene, and one intronic deletion of CALN1 gene. The present findings highlight the efficacy of combined cytogenetic and targeted mutation screening to improve the diagnostic yield in patient with ISs.

Published
2014

283. ZEB2, a new candidate gene for asplenia

Author

Massimiliano Rossi, Patrick Edery, Linda Pons, Marie-Pierre Cordier, Sophie Dupuis-Girod, BMC, Ed., Service de Génétique, Hospices Civils de Lyon (HCL)-Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Groupe Hospitalier Est, Translational and Integrative Group in Epilepsy Research (TIGER), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Service de Génétique, and Hospices Civils de Lyon (HCL)-Groupe Hospitalier Est-Hospices Civils de Lyon (HCL)-Hôpital Louis Pradel [CHU - HCL]

Subjects
Microcephaly, Pathology, medicine.medical_specialty, Candidate gene, Asplenia, Mowat–Wilson syndrome, Spleen, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, Epilepsy, medicine, Mowat-Wilson syndrome, Genetics(clinical), Pharmacology (medical), Letter to the Editor, Genetics (clinical), ZEB2, Medicine(all), Genetics, [SDV.GEN]Life Sciences [q-bio]/Genetics, General Medicine, Aplasia, medicine.disease, medicine.anatomical_structure, Etiology
Abstract

International audience; : Primary asplenia is a rare condition with poorly known etiology. Mowat-Wilson syndrome (MWS) is characterized by typical facial dysmorphisms, intellectual disability, microcephaly, epilepsy and the possible presence of internal organ malformations. It is caused by heterozygous mutations or deletions in the ZEB2 gene. Nearly 180 patients have been reported to date, but only one with asplenia. We report here spleen hypo/aplasia in 4 out of 6 MWS patients, with severe infectious complications for 3 of them. Our report shows that spleen hypo/aplasia is part of the MWS phenotype and makes ZEB2 a possible candidate gene for primary asplenia.

Published
2014

284. Collecting Cometary Dust Particles on Metal Blacks with The COSIMA Instrument Onboard ROSETTA

Author

Martin Hilchenbach, Massimiliano Rossi, Henning Fischer, Harald Krüger, Jochen Kissel, Cécile Engrand, Oleg Kulikov, Klaus Hornung, Yves Langevin, Eva Maria Mellado, Franz R. Krueger, CSNSM AS, Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), Institut d'astrophysique spatiale (IAS), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Spectrométrie Nucléaire et de Spectrométrie de Masse (CSNSM), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), and Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Sud - Paris 11 (UP11)

Subjects
High probability, Physics, MICROMETEORITES, [PHYS]Physics [physics], Cometary dust, [PHYS.ASTR.EP]Physics [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], Dust particles, Comet, Metal blacks, [SDU.ASTR.EP]Sciences of the Universe [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], Astronomy, ANTARCTIC SNOW, Astronomy and Astrophysics, Internal friction, EVOLUTION, Astrobiology, Space and Planetary Science, Rosetta mission, Collection efficiency
Abstract

International audience; After a brief review of the instrument development and materials selection for collecting cometary dust in the vicinity of comet 67/P Churyumov-Gerasimenko we focus on laboratory verification for the capability of metal black targets to decelerate and capture dust particles (velocities in the order of 100 m/s; sizes of some 10 mu m). The results indicate that particles between 10 and 100 mu m size can be collected with high probability. Two basic mechanisms of energy dissipation upon impact could be identified: By internal friction within a highly structured dust and within the black's nanostructure. In addition to the actual ROSETTA mission the data presented here might have a more general relevance for future, similar in-situ investigations. (C) 2014 Elsevier Ltd. All rights reserved.

Published
2014

286. Irbesartan Effects on Renal Function in Patients with Renal Impairment and Hypertension: A Drug-Withdrawal Study

Author

Piercarmine Cardace, Luigi Albanese, Carlo Vigorito, Massimiliano Rossi, Maria Leonarda De Rosa, Alessandro De Cristofaro, and Antonio Baiano

Subjects
Adult, Male, medicine.medical_specialty, medicine.drug_class, Urology, Tetrazoles, Renal function, Blood Pressure, Kidney Function Tests, urologic and male genital diseases, Drug Administration Schedule, Placebos, Irbesartan, medicine, Humans, Renal Insufficiency, Antihypertensive drug, Antihypertensive Agents, Aged, Pharmacology, urogenital system, business.industry, Biphenyl Compounds, Effective renal plasma flow, Middle Aged, medicine.disease, Angiotensin II, female genital diseases and pregnancy complications, Surgery, Proteinuria, Blood pressure, Tolerability, Creatinine, Hypertension, Drug Therapy, Combination, Female, Cardiology and Cardiovascular Medicine, business, Kidney disease, medicine.drug
Abstract

The blood-pressure lowering activity, tolerability, and safety of irbesartan was evaluated in 52 hypertensive patients with chronic renal insufficiency. After a 3-week placebo period, once-daily irbesartan was administered for 12 weeks at a daily dose of 150 mg titrated to 300 mg. A second, non-angiotensin-converting enzyme inhibitor, antihypertensive drug was added after 8 weeks as needed. Twenty-four-hour creatinine clearance was determined and renal clearance studies of inulin and para-aminohippurate were done in a subset of 11 patients. Trough sitting blood pressures were reduced at the end of the first week in all groups. At weeks 4, 8, and 12 the reductions in systolic blood pressure/diastolic blood pressure averaged -11.9/-8.7, -10.8/-9.4, and -14.7/-12.1 mm Hg in patients with mild renal insufficiency and -7.7/-6.3, -13.1/-11.8, and -14.1/-10.6 mm Hg in patients with moderate-to-severe renal insufficiency. Creatinine clearance, glomerular filtration rate, and effective renal plasma flow were stable. Irbesartan was withdrawn in only five patients because of adverse clinical or laboratory experience. Hyperkalemia (>6 mEq/l) requiring discontinuation of irbesartan occurred in only one patient. Once-daily irbesartan given as monotherapy at dose of 150-300 mg or in combination with other antihypertensive drugs is effective in reducing blood pressure in hypertensive patients with chronic renal disease. Irbesartan regimens are well tolerated in all groups. In addition, the blood pressure-lowering effect of irbesartan is accompanied by a significant reduction in proteinuria in patients with chronic renal insufficiency.

Published
2001

288. Liver transplantation in defects of cholesterol biosynthesis: the case of lathosterolosis

Author

Massimiliano Rossi, P.L. Calvo, Marco Spada, Gaetano Corso, Andrea Brunati, Maurizio Baldi, Antonio Amoroso, Ezio David, Giancarlo Parenti, Renato Romagnoli, Angela Pucci, Mauro Salizzoni, Giulia Carbonaro, Calvo, Pl, Brunati, A, Spada, M, Romagnoli, R, Corso, G, Parenti, Giancarlo, Rossi, M, Baldi, M, Carbonaro, G, David, E, Pucci, A, Amoroso, A, and Salizzoni, M.

Subjects
medicine.medical_specialty, Oxidoreductases Acting on CH-CH Group Donors, Steroid Metabolism, Inborn Errors, medicine.medical_treatment, Lathosterol, Liver transplantation, White matter, chemistry.chemical_compound, Liver disease, Cataracts, Cholestasis, Internal medicine, Intellectual Disability, medicine, Immunology and Allergy, Humans, Pharmacology (medical), Abnormalities, Multiple, lathosterolosis, Transplantation, business.industry, Lathosterolosis, Syndrome, medicine.disease, Prognosis, Magnetic Resonance Imaging, Surgery, Liver Transplantation, inherited metabolic disorders, medicine.anatomical_structure, Cholesterol, chemistry, Child, Preschool, Cardiology, Female, liver transplantation, business
Abstract

We report the outcome of liver transplantation (LT) in the only surviving patient with lathosterolosis, a defect of cholesterol biosynthesis characterized by high lathosterol levels associated with progressive cholestasis, multiple congenital anomalies and mental retardation. From her diagnosis at age 2 she had shown autistic behavior, was unable to walk unaided and her sight was impaired by cataracts. By age 7 she developed end-stage liver disease. After a soul-searching discussion within the transplantation team, she was treated with LT as this represented her only lifesaving option. At 1-year follow-up, her lathosterol levels had returned to normal (0.61 mg/dL from 13.04 ± 2.65) and her nutrition improved. She began exploring her environment and walking by holding onto an adult's hand and then independently. Her brain magnetic resonance imaging (MRI) had shown a normal picture at age 1, whereas a volume reduction of white matter with ex vacuo ventricular dilatation and defective myelinization were observed before transplant. At 5-year follow-up, a complete biochemical recovery, an arrest of mental deterioration and a stable MRI picture were achieved, with a return to her every day life albeit with limitations. Timely liver transplant in defects of cholesterol biosynthesis might arrest the progression of neurological damage.

Published
2013

289. Ultrasound-induced acoustophoretic motion of microparticles in three dimensions

Author

Henrik Bruus, Peter Barkholt Muller, Massimiliano Rossi, Alvaro Marin, Christian J. Kähler, Per Augustsson, Rune Barnkob, and Thomas Laurell

Subjects
Physics, Microchannel, Fluid Dynamics (physics.flu-dyn), FOS: Physical sciences, Physics - Fluid Dynamics, Mechanics, Physics::Fluid Dynamics, symbols.namesake, Acoustic streaming, Radiation pressure, Drag, Particle tracking velocimetry, symbols, Rayleigh scattering, Acoustic radiation force, Magnetosphere particle motion
Abstract

We derive analytical expressions for the three-dimensional (3D) acoustophoretic motion of spherical microparticles in rectangular microchannels. The motion is generated by the acoustic radiation force and the acoustic streaming-induced drag force. In contrast to the classical theory of Rayleigh streaming in shallow, infinite, parallel-plate channels, our theory does include the effect of the microchannel side walls. The resulting predictions agree well with numerics and experimental measurements of the acoustophoretic motion of polystyrene spheres with nominal diameters of 0.537 um and 5.33 um. The 3D particle motion was recorded using astigmatism particle tracking velocimetry under controlled thermal and acoustic conditions in a long, straight, rectangular microchannel actuated in one of its transverse standing ultrasound-wave resonance modes with one or two half-wavelengths. The acoustic energy density is calibrated in situ based on measurements of the radiation dominated motion of large 5-um-diam particles, allowing for quantitative comparison between theoretical predictions and measurements of the streaming induced motion of small 0.5-um-diam particles., 13 pages, 8 figures, Revtex 4.1

Published
2013

290. Molecular and clinical characterization of 25 individuals with exonic deletions of NRXN1 and comprehensive review of the literature

Author

Frédéric Bilan, Armand Bottani, Damien L. Bruno, Arie van Haeringen, Stylianos E. Antonarakis, Erica H. Gerkes, Brigitte Gilbert-Dussardier, Audrey Labalme, Stefania Gimelli, Claudia A. L. Ruivenkamp, Howard R. Slater, Alain Kitzis, Trijnie Dijkhuizen, Ann-Charlotte Thuresson, Marianne Till, Devika Ganesamoorthy, Damien Sanlaville, Christele Dubourgm, Conny M. A. van Ravenswaaij-Arts, Laurent Pasquier, Britt-Marie Anderlid, Marjolein Kriek, Massimiliano Rossi, Jacqueline Schoumans, Mats Eriksson, Frédérique Béna, Maryline Gagnebin, Michel Guipponi, Zornitza Stark, Génétique médicale, Hôpitaux Universitaires de Genève (HUG), Department of Genetics, Genetic Health Services Victoria, Department of Obstetrics and Gynecology, University of Oulu-Institute of Clinical Medicine, Department of Immunology, Genetics and Pathology [Uppsala, Sueden] (IGP), Uppsala University, Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, Service de Génétique, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Department of Human Genetics, Radboud University Medical Center [Nijmegen], Center for Medical Genetics, Victorian Clinical Genetics Services, Ethical, Legal, Social Issues in Genetics (ELSI), and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )

Subjects
[SDV]Life Sciences [q-bio], VARIANTS, Bioinformatics, Cell Adhesion Molecules, Neuronal/genetics, Cohort Studies, neurexin, 0302 clinical medicine, Intellectual disability, SCHIZOPHRENIA, Nerve Tissue Proteins/genetics, HUMAN GENOME, ddc:576.5, Copy-number variation, exon, deletion, Neural Cell Adhesion Molecules, Genetics (clinical), Sequence Deletion, seizures, Genetics, 0303 health sciences, Exons, Hypotonia, 3. Good health, Psychiatry and Mental health, Autism spectrum disorder, SEVERE DEVELOPMENTAL DELAY, medicine.symptom, Haploinsufficiency, Seizures/genetics, Autistic Disorder/genetics, Heterozygote, GENES, RARE DELETIONS, Cell Adhesion Molecules, Neuronal, review, autism, Nerve Tissue Proteins, Biology, Structural variation, 03 medical and health sciences, Cellular and Molecular Neuroscience, NRXN1, medicine, Humans, Expressivity (genetics), Autistic Disorder, 030304 developmental biology, COPY NUMBER VARIATION, HIGH-FREQUENCY, AUTISM SPECTRUM DISORDER, Calcium-Binding Proteins, medicine.disease, Karyotyping, Autism, 030217 neurology & neurosurgery, MENTAL-RETARDATION
Abstract

This study aimed to elucidate the observed variable phenotypic expressivity associated with NRXN1 (Neurexin 1) haploinsufficiency by analyses of the largest cohort of patients with NRXN1 exonic deletions described to date and by comprehensively reviewing all comparable copy number variants in all disease cohorts that have been published in the peer reviewed literature (30 separate papers in all). Assessment of the clinical details in 25 previously undescribed individuals with NRXN1 exonic deletions demonstrated recurrent phenotypic features consisting of moderate to severe intellectual disability (91%), severe language delay (81%), autism spectrum disorder (65%), seizures (43%), and hypotonia (38%). These showed considerable overlap with previously reported NRXN1-deletion associated phenotypes in terms of both spectrum and frequency. However, we did not find evidence for an association between deletions involving the -isoform of neurexin-1 and increased head size, as was recently published in four cases with a deletion involving the C-terminus of NRXN1. We identified additional rare copy number variants in 20% of cases. This study supports a pathogenic role for heterozygous exonic deletions of NRXN1 in neurodevelopmental disorders. The additional rare copy number variants identified may act as possible phenotypic modifiers as suggested in a recent digenic model of neurodevelopmental disorders. (c) 2013 Wiley Periodicals, Inc.

Published
2013

291. Cost-effective multispectral three-mirrors anastigmat sensor for high-performance surveillance applications using electroformed free-form mirrors

Author

Ivan Ferrario, P. Zago, W. Glage, Robert Banham, V. Syvokin, I. Neil, R. Formaro, S. Moretti, D. Blandino, G. Borghi, Giuseppe Valsecchi, A. Sposito, A. Ritucci, Massimiliano Rossi, N. Missaglia, and Fabio Zocchi

Subjects
Materials science, business.industry, Stray light, Multispectral image, Anastigmat, Three-mirror anastigmat, Field of view, law.invention, Telescope, Optics, law, Electroforming, Focal length, Optoelectronics, business
Abstract

A lightweight single-aperture and multi-spectral sensor operating from Visible to LWIR has been designed, manufactured and tested exploiting a Three Mirror Anastigmat (TMA) telescope featuring thin free-form mirrors electroformed from negative masters. Manufacturing complexity is in place only for the master realization, the contribution of which to the sensor cost decreases with the number of replicas. The TMA, suitable for airborne surveillance applications, has F/no. 1.4, focal length 136 mm and field of view 4.3° × 3.1°, and provides two channels, in the MWIR-LWIR and in the visible waveband. The nominal contrast is better than 75% in the visible at 25 cycles/mm. Electroformed 1 mm thick mirrors keep the sensor mass below 3 kg. Stray light and thermo-structural design has been done to comply with airborne conditions.

Published
2013

292. Novel Comprehensive Diagnostic Strategy in Pitt-Hopkins Syndrome: Clinical Score and Further Delineation of the TCF4 Mutational Spectrum

Author

Dragana Josifova, Corinne Metay, Juliette Piard, Sandra Whalen, Didier Lacombe, Oana Moldovan, Martine Le Merrer, Delphine Héron, Salim Aftimos, Michel Goossens, Irina Giurgea, Patrick Edery, Marlène Rio, Patrícia Dias, Franc Oise Devillard, Gabriela Soares, Lydie Burglen, Fabienne Giuliano, Grazia M.S. Mancini, Sophie Dupuis-Girod, Massimiliano Rossi, Lionel Van Maldergem, Damien Sanlaville, Loïc Drévillon, Nicole Philip, Audrey Briand-Suleau, Richard Fischer, Michelle Mathieu-Dramard, Alexandra Afenjar, Perrine Charles, Cyril Mignot, Johanna M. van Hagen, Thierry Gaillon, Audrey Putoux, Aurélia Jacquette, Jeanne Amiel, Alice Goldenberg, Human genetics, and Other Research

Subjects
Male, Adolescent, Genotype, Mutation, Missense, Haploinsufficiency, Pitt–Hopkins syndrome, Biology, medicine.disease_cause, Bioinformatics, Severity of Illness Index, Transcription Factor 4, Intellectual Disability, Angelman syndrome, Databases, Genetic, Genetics, medicine, Humans, Hyperventilation, Missense mutation, Child, Genetic Association Studies, Genetics (clinical), Sequence Deletion, Mutation, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Sequence Inversion, Molecular pathology, Point mutation, Facies, Genetic Variation, Infant, medicine.disease, Stop codon, Protein Structure, Tertiary, Phenotype, Haplotypes, Child, Preschool, Female, Chromosomes, Human, Pair 18, Transcription Factors
Abstract

Pitt-Hopkins syndrome (PTHS), characterized by severe intellectual disability and typical facial gestalt, is part of the clinical spectrum of Rett-like syndromes. TCF4, encoding a basic helix-loop-helix (bHLH) transcription factor, was identified as the disease-causing gene with de novo molecular defects. While PTHS appears to be a recognizable clinical entity, it seems to remain underdiagnosed, especially when facial gestalt is less typical. With the aim to facilitate the diagnosis of PTHS and to increase its rate and specificity, we have investigated 33 novel patients and defined a Clinical Diagnosis Score. Analysis of 112 individuals (79 previously reported and 33 novel patients) allowed us to delineate the TCF4 mutational spectrum, with 40% point mutations, 30% small deletions/insertions, and 30% deletions. Most of these were private mutations and generated premature stop codons. Missense mutations were localized in the bHLH domain, which is a mutational hotspot. No obvious difference was observed between patients harboring truncating, missense mutations, or deletions, further supporting TCF4 haploinsufficiency as the molecular mechanism underlying PTHS. In this study, we have summarized the current knowledge of TCF4 molecular pathology, reported all the mutations in the TCF4 database (http://www.LOVD.nl/TCF4), and present a novel and comprehensive diagnostic strategy for PTHS.

Published
2012

293. Development and testing of the eROSITA mirror modules

Author

Elmar Pfeffermann, Luigina Arcangeli, Michael Freyberg, Wolfgang Burkert, Josef Eder, Gisela Hartner, Fabio Marioni, Peter Predehl, Dervis Vernani, A. Ritucci, Andrea Borroni, Peter Friedrich, Gabriele Grisoni, G. Borghi, Vadim Burwitz, Oberto Citterio, Giuseppe Valsecchi, Ivan Ferrario, Heinrich Bräuninger, Bernd Budau, and Massimiliano Rossi

Subjects
Physics, Spacecraft, business.industry, Stray light, X-ray telescope, law.invention, Telescope, Optics, law, Bundle, Focal length, Angular resolution, business, Image resolution
Abstract

MPE will provide the X-ray Survey Telescope eROSITA for the Russian Spektrum-Roentgen-Gamma Mission to be launched in 2013. It consists of a compact bundle of 7 co-aligned mirror modules with a focal length of 1600 mm and 54 nested mirror shells each. Therefore, its sensitivity in terms of effective area, field-of-view (61'), and angular resolution (15" HEW on-axis) will yield a high grasp of about 1000 cm2 deg2 around 1 keV with an average angular resolution of ~26" HEW over the field-of-view (30" including optical and spacecraft error contributions). After an extended test program on single mirror shells, assembled test modules (6 shells) and a qualification model we have now started integration of flight mirror modules. We give a resume on the development and test program including key improvements to the shell integration method. Moreover, we report on the integration progress and present first results on the X-ray performance of partially integrated mirror modules.

Published
2011

295. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus

Author

Stephen W. Scherer, Mònica Gratacòs, Kari Stefansson, Muriel Holder, Unnur Thorsteinsdottir, Lukas Forer, Katharina M. Roetzer, Josette Lucas, Claudia Schurmann, Satu Kaksonen, Armand Valsesia, Carina Wallgren-Pettersson, Barbara Leube, Alexandra I. F. Blakemore, Alexandre Moerman, Marco Belfiore, Anne Faudet, Dominique Gaillard, Roberto Ravazzolo, Dominique Bonneau, Marjo-Riitta Järvelin, Yongguo Yu, Louis Vallée, Bénédicte Demeer, Sophie Visvikis-Siest, Frédérique Béna, Brigitte H. W. Faas, Benoit Arveiler, Georg Homuth, Charles Coutton, Bénédicte de Fréminville, Giorgio Gimelli, Xavier Estivill, Richard I. Fisher, Stefania Gimelli, Wendy Roberts, Jacques S. Beckmann, Emilie Landais, Orah S. Platt, Robin G. Walters, Gudmar Thorleifsson, Alexandre Reymond, Anna-Liisa Hartikainen, Solenn Legallic, James F. Gusella, Peter Vollenweider, Gian Paolo Ramelli, Tõnu Esko, Boris Keren, Nine V A M Knoers, Fanny Morice-Picard, Dominique Campion, Odile Boute, Evica Rajcan-Separovic, Rolph Pfundt, Nathalie Bednarek, Martine Doco-Fenzy, Suzanne M E Lewis, Gérard Didelot, Mylène Beri, Engilbert Sigurdsson, Véronique Satre, Audrey Labalme, Carola Tengstrom, Florian Kronenberg, Florence Petit, Simon Zwolinksi, Philippe Froguel, Paul Elliott, Dorothée Cailley, Christian R. Marshall, Bruno Leheup, Klaus Dieterich, Janina S. Ried, Sylvie Jaillard, Armand Bottani, Stylianos E. Antonarakis, Elisabetta Lapi, Jean-Christophe Cuvellier, Robert M. Witwicki, Gérard Waeber, Christèle Dubourg, Marion Gérard, Lachlan J. M. Coin, Magalie Barth, Anita Kloss-Brandstätter, Vincent Mooser, Cristóbal Richart, Giuseppe Merla, Bénédicte Duban-Bedu, Yiping Shen, Ants Kurg, Audrey Guilmatre, Juliane Hoyer, Susana Jiménez-Murcia, Mafalda Mucciolo, Bai-Lin Wu, Alessandra Ferrarini, Séverine Drunat, Yves Alembik, Páll Magnússon, Han G. Brunner, Maria Antonietta Mencarelli, Dominique Descamps, R. Frank Kooy, Azzedine Aboura, Valérie Layet, Sven Bergmann, Thomas Meitinger, Peter M. Kroisel, Nathalie Van der Aa, Olivier Guillin, Michèle Mathieu-Dramard, Zoltán Kutalik, Elisabeth Flori, Laurent Pasquier, André Reis, Noam D. Beckmann, Bertrand Isidor, Delphine Héron, Philippe Jonveaux, Sergi Villatoro Gomez, Ann Nordgren, José Manuel Fernández-Real, Florence Fellmann, Fernando Fernández-Aranda, Laurence Faivre, Dimitri J. Stavropoulos, Katrin Männik, Christian Gieger, Evald Saemundsen, Agnès Guichet, Jean-Marie Cuisset, R. Touraine, Laura Bernardini, Marie-Ange Delrue, Alessandra Renieri, Omar Gustafsson, Flore Zufferey, David A. Koolen, Massimiliano Rossi, Jacqueline Chrast, Ghislaine Plessis, Faida Walha, Joris Andrieux, Ellen van Binsbergen, Albert David, Catherine Vincent-Delorme, Cédric Le Caignec, Jean Chiesa, Ndeye Coumba Ndiaye, Geraldine Joly Helas, Damien Sanlaville, Anita Rauch, Louise Harewood, Mark I. McCarthy, Bridget A. Fernandez, Sébastien Jacquemont, Hreinn Stefansson, Anneke T. Vulto-van Silfhout, Zdenek Jaros, Matthias Nauck, Hans J. Grabe, Sonia Bouquillon, Mieke M. van Haelst, Andres Metspalu, Loyse Hippolyte, Patrick Callier, Bert B.A. de Vries, Francisco J. Tinahones, Nicole de Leeuw, Julia S. El-Sayed Moustafa, Claudine Rieubland, Kay D. MacDermot, Vittoria Disciglio, Henry Völzke, Caroline Rooryck, Bettina Blaumeiser, Danielle Martinet, Marie-Claude Addor, Bruno Delobel, Jacquemont, S, Reymond, A, Zufferey, F, Harewood, L, Walters, Rg, Kutalik, Z, Martinet, D, Shen, Y, Valsesia, A, Beckmann, Nd, Thorleifsson, G, Belfiore, M, Bouquillon, S, Campion, D, de Leeuw, N, de Vries, Bb, Esko, T, Fernandez, Ba, Fernández-Aranda, F, Fernández-Real, Jm, Gratacòs, M, Guilmatre, A, Hoyer, J, Jarvelin, Mr, Kooy, Rf, Kurg, A, Le Caignec, C, Männik, K, Platt, O, Sanlaville, D, Van Haelst, Mm, Villatoro Gomez, S, Walha, F, Wu, Bl, Yu, Y, Aboura, A, Addor, Mc, Alembik, Y, Antonarakis, Se, Arveiler, B, Barth, M, Bednarek, N, Béna, F, Bergmann, S, Beri, M, Bernardini, L, Blaumeiser, B, Bonneau, D, Bottani, A, Boute, O, Brunner, Hg, Cailley, D, Callier, P, Chiesa, J, Chrast, J, Coin, L, Coutton, C, Cuisset, Jm, Cuvellier, Jc, David, A, de Freminville, B, Delobel, B, Delrue, Ma, Demeer, B, Descamps, D, Didelot, G, Dieterich, K, Disciglio, V, Doco-Fenzy, M, Drunat, S, Duban-Bedu, B, Dubourg, C, El-Sayed Moustafa, J, Elliott, P, Faas, Bh, Faivre, L, Faudet, A, Fellmann, F, Ferrarini, A, Fisher, R, Flori, E, Forer, L, Gaillard, D, Gerard, M, Gieger, C, Gimelli, S, Gimelli, G, Grabe, Hj, Guichet, A, Guillin, O, Hartikainen, Al, Heron, D, Hippolyte, L, Holder, M, Homuth, G, Isidor, B, Jaillard, S, Jaros, Z, Jiménez-Murcia, S, Helas, Gj, Jonveaux, P, Kaksonen, S, Keren, B, Kloss-Brandstätter, A, Knoers, Nv, Koolen, Da, Kroisel, Pm, Kronenberg, F, Labalme, A, Landais, E, Lapi, E, Layet, V, Legallic, S, Leheup, B, Leube, B, Lewis, S, Lucas, J, Macdermot, Kd, Magnusson, P, Marshall, C, Mathieu-Dramard, M, Mccarthy, Mi, Meitinger, T, Mencarelli, Ma, Merla, G, Moerman, A, Mooser, V, Morice-Picard, F, Mucciolo, M, Nauck, M, Ndiaye, Nc, Nordgren, A, Pasquier, L, Petit, F, Pfundt, R, Plessis, G, Rajcan-Separovic, E, Ramelli, Gp, Rauch, A, Ravazzolo, R, Reis, A, Renieri, A, Richart, C, Ried, J, Rieubland, C, Roberts, W, Roetzer, Km, Rooryck, C, Rossi, M, Saemundsen, E, Satre, V, Schurmann, C, Sigurdsson, E, Stavropoulos, Dj, Stefansson, H, Tengström, C, Thorsteinsdóttir, U, Tinahones, Fj, Touraine, R, Vallée, L, van Binsbergen, E, Van der Aa, N, Vincent-Delorme, C, Visvikis-Siest, S, Vollenweider, P, Völzke, H, Vulto-van Silfhout, At, Waeber, G, Wallgren-Pettersson, C, Witwicki, Rm, Zwolinksi, S, Andrieux, J, Estivill, X, Gusella, Jf, Gustafsson, O, Metspalu, A, Scherer, Sw, Stefansson, K, Blakemore, Ai, Beckmann, J, Froguel, P, Faculteit Medische Wetenschappen/UMCG, Service de génétique médicale, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL)-Université de Lausanne = University of Lausanne (UNIL), Department of Genomics of Common Disease, Imperial College London, Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Laboratory Medicine, Boston Children's Hospital, Center for Human Genetic Research, Massachusetts General Hospital [Boston], Ludwig Institute for Cancer Research, deCODE Genetics, deCODE genetics [Reykjavik], Laboratoire de Génétique Médicale, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Estonian Genome and Medicine, University of Tartu, Department of human genetics, Radboud University Medical Center [Nijmegen]-Nijmegen Centre for Molecular Life Sciences-Institute for Genetic and Metabolic Disorders, Institute of Molecular and Cell Biology, Disciplines of Genetics and Medicine, Memorial University of Newfoundland = Université Memorial de Terre-Neuve [St. John's, Canada] (MUN), Department of Psychiatry (IDIBELL), CIBERobn Fisiopatología de la Obesidad y Nutrición-University Hospital of Bellvitge, Section of Diabetes, Endocrinology and Nutrition, University Hospital of Girona-Biomedical Research Institute 'Dr Josep Trueta'-CIBERobn Fisiopatología de la Obesidad y Nutrición, Center for Genomic Regulation (CRG-UPF), CIBER de Epidemiología y Salud Pública (CIBERESP), Institute of Human Genetics [Erlangen, Allemagne], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Department of child and adolescent health, University of Oulu-Institute of Health Sciences and Biocenter Oulu-National Institute for Health and Welfare [Helsinki], Antwerp University Hospital [Edegem] (UZA), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, University Medical Center [Utrecht], Institutes of Biomedical Science, Fudan University [Shanghai]-Children's Hospital, Shanghai Children's Medical Center, Département de génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de cytogénétique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Génétique médicale, Hôpitaux Universitaires de Genève (HUG), Maladies Rares - Génétique et Métabolisme (MRGM), Université Bordeaux Segalen - Bordeaux 2-Hôpital Pellegrin-Service de Génétique Médicale du CHU de Bordeaux, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Université de Reims Champagne-Ardenne (URCA), Department of Molecular Genetics, Weizmann Institute of Science [Rehovot, Israël], Service de Génétique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Mendel Laboratory, Istituto di Ricovero e Cura a Carattere Scientifico, Ospedale Casa Sollievo della Sofferenza [San Giovanni Rotondo] (IRCCS), Service de Génétique clinique, Laboratoire de cytogénétique (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de Cytogénétique, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Département de génétique et procréation, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-faculté de médecine-pharmacie, AGeing and IMagery (AGIM), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biochimie et génétique moléculaire, CHU Grenoble, Service de Neuropédiatrie, Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de génétique, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre de Génétique Chromosomique, Hôpital Saint Vincent de Paul-Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), CHU Amiens-Picardie, Centre Hospitalier de Béthune (CH Béthune), GHT de l'Artois, Service de Génétique Clinique, Department of Biotechnology, Università degli Studi di Siena = University of Siena (UNISI)-Medical Genetics, Service de Génétique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Department of Epidemiology and Public Health, Department of Human Genetics [Nijmegen], Radboud University Medical Center [Nijmegen], Department of Experimental Cardiology, Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Heart Failure Research Center (HFRC), CHU Pitié-Salpêtrière [AP-HP], Institute of human genetics, International Centre for Life, Division of genetic epidemiology, HMNC Brain Health-Molecular and Clinical Pharmacology-Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (CAS), Department of Obstetrics and Gynecology, University of Oulu-Institute of Clinical Medicine, Laboratorio di citogenetica, G. Gaslini Institute, Department of Psychiatry and Psychotherapy, Universität Greifswald - University of Greifswald, Interfaculty Institute for Genetics and Functional Genomics, Abteilung für Kinder und Jugendheilkunde, Landesklinikum Waldviertel Zwettl, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), The Habilitation Unit of Folkhalsan, Medical University Graz, Medical Genetics Unit, Children's Hospital Anna Meyer, Unité de Cytogénétique et Génétique Médicale, Groupe Hospitalier du Havre-Hôpital Gustave Flaubert, Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Institute of Human Genetics and Anthropology, Heinrich-Heine University Hospital Duesseldorf, Child and Family Research Institute-University of British Columbia (UBC), North West Thames Regional Genetics Service, Northwick Park & St Marks Hospital, Child and Adolescent Psychiatry, Landspitali University Hospital, Program in Genetics and Genomic Biology, Hospital for Sick Children-University of Toronto McLaughlin Centre, Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), University of Oxford, The Wellcome Trust Centre for Human Genetics [Oxford], Institute of Human Genetics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz Zentrum München = German Research Center for Environmental Health, Genetics, GlaxoSmithKline R&D, GlaxoSmithKline, Institute of Clinical Chemistry and Laboratory Medicine, Génétique cardiovasculaire (GC), Université Henri Poincaré - Nancy 1 (UHP), Molecular Medicine and Surgery department, Karolinska Institutet [Stockholm], Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Department of Pathology, Division of pediatrics, Ospedale San Giovanni, Institute of Medical Genetics, Universität Zürich [Zürich] = University of Zurich (UZH), Department of pediatrics and CEBR, Università degli studi di Genova = University of Genoa (UniGe)-G. Gaslini Institute, Department of Internal Medicine, Universitat Rovira i Virgili-University Hospital Juan XXIII-Instituto Salud Carlos III-Ciber Fisiopatologia Obesidad y Nutricion (CIBEROBN), Division of Human Genetics, Department of Paediatrics, Inselspital-University of Bern, Autism Research Unit, The Hospital for sick children [Toronto] (SickKids)-University of Toronto, State Diagnostic, Counseling Center, University of Iceland [Reykjavik], Department of Pediatric Laboratory Medicine, Hospital for Sick Children, Genetic Services, Rinnekoti Research Foundation, Department of Endocrinology and Nutrition, Instituto Salud Carlos III-Clinic Hospital of Virgen de la Victoria-Ciber Fisiopatologia y Nutricion (CIBEROBN), Centre de Maladies Rares, Anomalies du Développement Nord de France-CH Arras - CHRU Lille, Institute for Community Medicine, Department of Medical and Clinical Genetics [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, The Centre for Applied Genomics, Toronto, The Hospital for sick children [Toronto] (SickKids)-University of Toronto-Department of Molecular Genetics-McLaughlin Centre, Institut de biologie de Lille - UMS 3702 (IBL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Leenaards Foundation Prize (SJ, DM and AR), the Jérôme Lejeune Foundation (AR), the Telethon Action Suisse Foundation (AR), the Swiss National Science Foundation (AR, JSB, SB and SEA), a SNSF Sinergia grant (SJ, DM, SB, JSB and AR), the European Commission anEUploidy Integrated Project grant 037627 (AR, SB, XE, HGB and SEA), the Ludwig Institute for Cancer Research (AV), the Swiss Institute of Bioinformatics (SB, ZK), an Imperial College Dept of Medicine PhD studentship (JSe-SM), the Comprehensive Biomedical Research Centre, Imperial College Healthcare NHS Trust, and the National Institute for Health Research (PE), the Wellcome Trust and the Medical Research Council (AIFB and PF), the Instituto de Salud Carlos III (ISCIII)-FIS, the German Mental Retardation Network funded through a grant of the German Federal Ministry of Education and Research (NGFNplus 01GS08160) to A Reis and European Union-FEDER (PI081714, PS09/01778), SAF2008-02278 (XE, MG, FFA), the Belgian National Fund for Scientific Research - Flanders (NVA, RFK), the Dutch Organisation for Health Research and Development (ZONMW grant 917-86-319) and Hersenstichting Nederland (BBAdV), grant 81000346 from the Chinese National Natural Science Foundation (YGY), the Simons Foundation Autism Research Initiative, Autism Speaks and NIH grant GM061354 (JFG), and the OENB grant 13059 (AK-B). YS holds a Young Investigator Award from the Children's Tumor Foundation and Catalyst Award from Harvard Medical School, and BLW, a Fudan Scholar Research Award from Fudan University, a grant from Chinese National '973' project on Population and Health (2010CB529601) and a grant from Science and Technology Council of Shanghai (09JC1402400). ERS and SL, recipients of the Michael Smith Foundation for Health Research Scholar award, acknowledge the CIHR MOP 74502 operational grant. EGCUT received support from the EU Centre of Excellence in Genomics and FP7 grants #201413 and #245536, from Estonian Government SF0180142s08, SF0180026s09 and SF0180027s10 (AM, KM, AK). The Helmholtz Zentrum Munich and the State of Bavaria financed KORA, also supported by the German National Genome Research Network (NGFN-2 and NGFNPlus: 01GS0823), the German Federal Ministry of Education and Research (BMBF), and the Munich Center of Health Sciences (MC Health, LMUinnovativ). CIBEROBN and CIBERESP are initiatives of ISCIII (Spain). SWS holds the GlaxoSmithKline-Canadian Institutes of Health (CIHR) Chair in Genetics, Genomics at the University of Toronto and the Hospital for Sick Children and is supported by Genome Canada and the McLaughlin Centre. deCODE was funded in part by NIH grant MH071425 (KS), EU grant HEALTH-2007-2.2.1-10-223423 (Project PsychCNV) and EU grant IMI-JU-NewMeds., Centre de génomique intégrative, Université de Lausanne (UNIL), Swiss Institute of Bioinformatics (SIB), Swiss Institute of Bioinformatics, Memorial University of Newfoundland [St. John's], Friedrich Alexander University [Erlangen-Nürnberg], Service d'ORL et de Chirurgie Cervicofaciale, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Weizmann Institute of Science, IRCCS Casa Sollievo della Sofferenza Hospital, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Hôpital Roger Salengro-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Saint-Etienne-Hôpital nord, Hôpital Saint Vincent de Paul-GHICL, Centre hospitalier de Béthune, Università degli Studi di Siena (UNISI)-Medical Genetics, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Department of Human Genetics, Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Innsbruck Medical University [Austria] (IMU)-HMNC Brain Health-Molecular and Clinical Pharmacology, Czech Academy of Sciences [Prague] (ASCR), University of Oxford [Oxford], Technische Universität München [München] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, University of Zürich [Zürich] (UZH), Universita degli studi di Genova -G. Gaslini Institute, University of Toronto-The Hospital for Sick Children, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, University of Toronto-The Hospital for Sick Children-Department of Molecular Genetics-McLaughlin Centre, Institut de biologie de Lille - IBL (IBLI), Université de Lille, Sciences et Technologies-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), De Villemeur, Hervé, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-École pratique des hautes études (EPHE), Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland., Other departments, Reymond, Alexandre, Antonarakis, Stylianos, Sloan Bena, Frédérique, Bottani, Armand, Callier, Patrick, Gimelli, Stefania, Merla, Giuseppe, Vollenweider, Peter, Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Joseph Fourier - Grenoble 1 (UJF)-Université Pierre Mendès France - Grenoble 2 (UPMF), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), University of Toronto-The Hospital for sick children [Toronto] (SickKids)-Department of Molecular Genetics-McLaughlin Centre, Université de Lille-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Aging, Transcription, Genetic, Adolescent, Adult, Aged, Body Height, Body Mass Index, Case-Control Studies, Child, Child, Preschool, Chromosomes, Human, Pair 16, Cohort Studies, Comparative Genomic Hybridization, Developmental Disabilities, Energy Metabolism, Europe, Female, Gene Dosage, Gene Duplication, Gene Expression Profiling, Genetic Predisposition to Disease, Genome-Wide Association Study, Head, Heterozygote, Humans, Infant, Infant, Newborn, Mental Disorders, Middle Aged, Mutation, North America, Obesity, Phenotype, RNA, Messenger, Sequence Deletion, Thinness, Young Adult, Physiology, RNA, Messenger/analysis/genetics, Genome-wide association study, HIDDEN-MARKOV MODEL, 0302 clinical medicine, Sequence Deletion/genetics, ddc:576.5, 0303 health sciences, education.field_of_study, Body Height/genetics, Genetic Predisposition to Disease/genetics, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, population characteristics, Chromosomes, Human, Pair 16/genetics, Human, Locus (genetics), Gene Duplication/genetics, Article, 03 medical and health sciences, Genetic, education, SNP GENOTYPING DATA, Thinness/genetics, [SDV.GEN]Life Sciences [q-bio]/Genetics, Pair 16, Case-control study, nutritional and metabolic diseases, social sciences, medicine.disease, DEPENDENT PROBE AMPLIFICATION, Human medicine, Body mass index, 030217 neurology & neurosurgery, Messenger, Obesity/genetics, FAILURE-TO-THRIVE, [SDV.GEN] Life Sciences [q-bio]/Genetics, Head/anatomy & histology, METABOLIC SYNDROME, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 2. Zero hunger, Genetics, Multidisciplinary, TIME QUANTITATIVE PCR, Failure to thrive, medicine.symptom, Underweight, Transcription, geographic locations, Mutation/genetics, Population, Biology, Chromosomes, 150 000 MR Techniques in Brain Function, medicine, Preschool, 030304 developmental biology, COPY NUMBER VARIATION, Mental Disorders/genetics, Energy Metabolism/genetics, RELATIVE QUANTIFICATION, Gene Dosage/genetics, Newborn, BODY-MASS INDEX, CIRCULAR BINARY SEGMENTATION, RNA, Genetics and epigenetic pathways of disease Genomic disorders and inherited multi-system disorders [NCMLS 6], human activities, Developmental Disabilities/genetics
Abstract

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field. Both obesity and being underweight have been associated with increased mortality. Underweight, defined as a body mass index (BMI) ≤ 18.5 kg per m(2) in adults and ≤ -2 standard deviations from the mean in children, is the main sign of a series of heterogeneous clinical conditions including failure to thrive, feeding and eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic variants underlying these clinical conditions have been reported. We previously showed that hemizygosity of a ∼600-kilobase (kb) region on the short arm of chromosome 16 causes a highly penetrant form of obesity that is often associated with hyperphagia and intellectual disabilities. Here we show that the corresponding reciprocal duplication is associated with being underweight. We identified 138 duplication carriers (including 132 novel cases and 108 unrelated carriers) from individuals clinically referred for developmental or intellectual disabilities (DD/ID) or psychiatric disorders, or recruited from population-based cohorts. These carriers show significantly reduced postnatal weight and BMI. Half of the boys younger than five years are underweight with a probable diagnosis of failure to thrive, whereas adult duplication carriers have an 8.3-fold increased risk of being clinically underweight. We observe a trend towards increased severity in males, as well as a depletion of male carriers among non-medically ascertained cases. These features are associated with an unusually high frequency of selective and restrictive eating behaviours and a significant reduction in head circumference. Each of the observed phenotypes is the converse of one reported in carriers of deletions at this locus. The phenotypes correlate with changes in transcript levels for genes mapping within the duplication but not in flanking regions. The reciprocal impact of these 16p11.2 copy-number variants indicates that severe obesity and being underweight could have mirror aetiologies, possibly through contrasting effects on energy balance. Leenaards Foundation Jerome Lejeune Foundation Telethon Action Suisse Foundation Swiss National Science Foundation European Commission 037627 QLG1-CT-2000-01643 Ludwig Institute for Cancer Research Swiss Institute of Bioinformatics Imperial College Department of Medicine Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust National Institute for Health Research Wellcome Trust Medical Research Council Instituto de Salud Carlos III (ISCIII)-FIS German Mental Retardation Network German Federal Ministry of Education and Research NGFNplus 01GS08160 European Union PI081714 PS09/01778 201413 245536 info:eu-repo/grantAgreement/EC/FP7/223423 Belgian National Fund for Scientific Research, Flanders Dutch Organisation for Health Research and Development (ZON-MW) 917-86-319 Hersenstichting Nederland (B.B.A.d.V.) Chinese National Natural Science Foundation 81000346 Simons Foundation Autism Research Initiative Autism Speaks NIH GM061354 MH071425 Oesterreichische Nationalbank (OENB) 13059 Children's Tumor Foundation Harvard Medical School Fudan University Chinese National '973' project on Population and Health 2010CB529601 Science and Technology Council of Shanghai 09JC1402400 Michael Smith Foundation for Health CIHR MOP 74502 Estonian Government SF0180142s08 SF0180026s09 SF0180027s10 Helmholtz Zentrum Munich State of Bavaria German National Genome Research Network 01GS0823 German Federal Ministry of Education and Research (BMBF) Munich Center of Health Sciences (MC Health, LMUinnovativ) Genome Canada McLaughlin Centre Academy of Finland 104781 120315 129269 1114194 University Hospital Oulu Biocenter University of Oulu, Finland 75617 NHLBI 5R01HL087679-02 1RL1MH083268-01 NIH/NIMH 5R01MH63706:02 ENGAGE project Medical Research Council, UK G0500539 G0600705 Academy of Finland Biocentrum Helsinki SAF2008-02278 HEALTH-F4-2007-201413

Published
2011

296. The Renpenning syndrome spectrum: new clinical insights supported by 13 new PQBP1-mutated males

Author

Sabine Sigaudy, Fabienne Giuliano, Massimiliano Rossi, D. Gérard, David Germanaud, Lucie Hertz-Pannier, Gérald Bussy, V. des Portes, Patricia Blanchet, R. Touraine, Pierre Sarda, Aurore Curie, Hélène Dollfus, V. Bennouna-Greene, Marie-Claire Vincent, Laboratoire sur le langage, le cerveau et la cognition (L2C2), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service NEUROSPIN (NEUROSPIN), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Service de génétique médicale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Laboratoire de Génétique Médicale (LGM), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions et dynamique des environnements de surface (IDES), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Service de Génétique et de Diagnostic Prénatal, Université de la Méditerranée - Aix-Marseille 2, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire de Génétique Médicale, and Université Louis Pasteur - Strasbourg I-AVENIR-Inserm-Hôpital de Hautepierre [Strasbourg]

Subjects
Adult, Male, Microcephaly, Pediatrics, medicine.medical_specialty, Adolescent, Genotype, Central nervous system disease, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Neuroimaging, Pregnancy, Genetics, medicine, Ankylosis, Humans, Child, Gyrification, Genetics (clinical), 030304 developmental biology, 0303 health sciences, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Cerebral Palsy, Brain, Nuclear Proteins, Progressive muscular atrophy, medicine.disease, 3. Good health, Mild short stature, Developmental disorder, DNA-Binding Proteins, Radiography, Phenotype, Child, Preschool, Mutation, Mental Retardation, X-Linked, Female, France, business, Carrier Proteins, Cognition Disorders, 030217 neurology & neurosurgery
Abstract

International audience; Since the first reports of polyglutamine-binding protein 1 (PQBP1) mutations in Renpenning syndrome and related disorders, the spectrum of PQBP1-linked clinical manifestations has been outlined from rare published case reports. The phenotypic description is often obtained from medical archives, and therefore, heterogeneous. Moreover, some aspects such as brain imaging or cognitive and behavioral functioning are rarely described. In this study, 13 PQBP1-mutated French patients were subjected to a standardized clinical, cognitive and behavioral assessment. Physical measurements of their relatives were also collected. We report on a recognizable clinical and radiological phenotype. All patients presented with microcephaly, leanness and mild short stature, relative to familial measurements. Three new clinical features are described: upper back progressive muscular atrophy, metacarpophalangeal ankylosis of the thumb and velar dysfunction. The specific facial dysmorphic features included at least four of the following signs: long triangular face, large ridged nose, half-depilated eyebrows, dysplastic or protruding ears and rough slightly sparse hair. An over-aged appearance was noticed in elderly patients. Cortical gyrification was normal based on available magnetic brain imaging of six patients. PQBP1-linked microcephaly (or Renpenning syndrome) is an X-linked mental retardation syndrome, which has clinically recognizable features.

Published
2010

297. Development and performance of grazing and normal incidence collectors for the HVM DPP and LPP sources

Author

Massimiliano Rossi, Giovanni Bianucci, Fabio Zocchi, A. Bragheri, Gian Luca Cassol, and B. Johnson

Subjects
Materials science, Temperature control, business.industry, Extreme ultraviolet lithography, Laser, High volume manufacturing, law.invention, Full width at half maximum, Optics, law, Extreme ultraviolet, Electroforming, Optoelectronics, Photolithography, business
Abstract

Media Lario Technologies (MLT), leveraging off its unique in-field collector experience, has designed the Grazing Incidence Collector (GIC) for the Sn-fueled Discharge Produced Plasma (DPP) source developed by Philips Extreme UV (PEUV) and XTREME technologies (XT) for High Volume Manufacturing (HVM) deployment. The performance of the HVM GIC described in this work shows a point-source collection efficiency of 24%, and is enabled by an integrated thermal control system designed to ensure optical stability for an absorbed thermal load of 6 kW. The GIC reflective layer has been custom tailored to match the debris mitigation strategy developed and characterized by PEUV and XT, supporting at least a 1-year lifetime proposition of the source-collector module. Leveraging off the experience gained in GIC, MLT is developing the processes to manufacture the Normal Incidence Collector (NIC) for Laser Produced Plasma (LPP) sources. Using its proprietary disruptive replication technology by electroforming, MLT is developing thermal management designs for NIC enabling stable operation at room temperature. This work reports on the performance of (symbol) 150 mm thermally managed NIC demonstrators. The mirror substrates have been integrated with new proprietary thermal management designs that are well suited to the electroformed mirrors. We also report on the reflectivity of the Mo/Si multilayer coated mirror, achieving maximum reflectivity values of 62% and a center wavelength (FWHM) of 13.52 nm, which demonstrates acceptable performance in an LPP NIC application.

Published
2010

298. Technologies for manufacturing of high angular resolution multilayer coated optics for future new hard x-ray missions: a status report

Author

Fabio Marioni, Dervis Vernani, G. Pareschi, Gabriele Grisoni, G. Tagliaferri, Stefano Basso, Giuseppe Valsecchi, G. Salmaso, Oberto Citterio, G. Borghi, E. Marchi Boscolo, Daniele Spiga, A. Ritucci, J. Kools, Massimiliano Rossi, Barbara Negri, and A. Orlandi

Subjects
Materials science, business.industry, X-ray optics, engineering.material, Sputter deposition, Metrology, Mandrel, Optics, Coating, Electroforming, engineering, Angular resolution, business, Surface finishing
Abstract

High throughput lightweight Hard X-ray Optics manufactured via electroforming replication process from supersmooth mandrels are the primary candidate for some of future New Hard X-ray missions. Media Lario Technologies (MLT) is the industrial enabler exploiting the electroforming technology initially applied for the ESA XMM-Newton mission and further developed in cooperation with Brera Astronomical Observatory (INAF/OAB). The current and ongoing development activities in Media Lario Technologies complement the electroforming technology with a suite of critical manufacturing and assembly of the Mirror Module Unit. In this paper, the progress on mandrels manufacturing, mirror shell replication, multilayer coating deposition, mirror module integration, and relevant metrology is reported in view of the upcoming production phase. Mandrel production is a key point in terms of performances and schedule; the results from of NiP prototype mandrels fabricated using a proprietary multistep surface finishing process are reported. The progress in the replication of ultrathin Nickel and Nickel-Cobalt substrates gold coated mirror shells is reported together with the results of MLT Magnetron Sputtering multilayer coating technology for the hard x-ray waveband and its application to W/Si. Due to the criticality of low thickness mirror handling, the integration concept has been refined and tested on prototype mechanical structures under full illumination UV vertical optical bench.

Published
2009

299. Optimization of multiplane ?PIV for wall shear stress and wall topography characterization

Author

Jerry Westerweel, Massimiliano Rossi, and Ralph Lindken

Subjects
Fluid Flow and Transfer Processes, Observational error, Materials science, business.industry, Monte Carlo method, Flow (psychology), Computational Mechanics, General Physics and Astronomy, Mechanics, Physics and Astronomy(all), Characterization (materials science), Physics::Fluid Dynamics, Optics, Particle image velocimetry, Mechanics of Materials, Shear stress, Boundary value problem, business, Velocity measurement
Abstract

Multiplane ?PIV can be utilized to determine the wall shear stress and wall topology from the measured flow over a structured surface. A theoretical model was developed to predict the measurement error for the surface topography and shear stress, based on a theoretical analysis of the precision in PIV measurements. The main parameters that affect the accuracy of the measurement are identified. The effect of different parameter settings is studied by means of Monte Carlo simulations, and the results are compared with an experimental test case. The results are used to determine the recommended parameter settings for this measurement approach.

Published
2009

300. Penile doppler ultrasound in patients with erectile dysfunction (ED): role of peak systolic velocity measured in the flaccid state in predicting arteriogenic ED and silent coronary artery disease

Author

Giovanni, Corona, Giorgio, Fagioli, Edoardo, Mannucci, Annadina, Romeo, Massimiliano, Rossi, Francesco, Lotti, Alessandra, Sforza, Stefano, Morittu, Valerio, Chiarini, Gianni, Casella, Giuseppe, Di Pasquale, Elisa, Bandini, Gianni, Forti, and Mario, Maggi

Subjects
Adult, Male, Tomography, Emission-Computed, Single-Photon, Adenosine, Coronary Disease, Comorbidity, Middle Aged, Cohort Studies, Impotence, Vasculogenic, Risk Factors, Exercise Test, Humans, Ultrasonography, Doppler, Color, Blood Flow Velocity, Aged, Penis
Abstract

The use of the penile peak systolic velocity (PSV) measured in the flaccid state during penile color Doppler ultrasound (PCDU) examination has been questioned without substantial evidence.To assess the validity of PSV measured in the flaccid state during PCDU, in patients consulting for erectile dysfunction (ED).A consecutive series of 1,346 (mean age 55.0 +/- 12.0 years) male patients was studied.All patients underwent PCDU performed both in the flaccid state and dynamic (after prostaglandin E1 stimulation) conditions. A subset of 20 subjects with uncomplicated type 2 diabetes underwent diagnostic testing for silent coronary heart disease by means of adenosine stress myocardial perfusion scintigraphy (SPECT). In these subjects penile arterial flow was simultaneously assessed by PCDU before and after systemic adenosine administration.Flaccid PSV showed a significant (r = 0.513, P0.0001) correlation with dynamic PSV. Receiver operating characteristic (ROC) curve analysis demonstrated that when a threshold of 13 cm/seconds was chosen, flaccid PSV was predictive for dynamic PSV25 and35 cm/seconds with an accuracy of 89% and 82%, respectively. Among the subset of patients who underwent SPECT, an impaired coronary flow reserve (ICFR) occurred in nine cases (45%). When the same threshold of13 cm/seconds was chosen, PSV before SPECT was predictive of ICFR with an accuracy of 80% (area under the ROC curve = 0.798 +/- 0.10; P0.05). After adjustment for confounders, anxiety symptoms were related to dynamic PSV (Adj. r = -0.154, P0.05) but not to flaccid PSV.Our results show that flow in the cavernosal arteries can be routinely evaluated by PCDU in the flaccid state. Performing PCDU only in the flaccid state allows identifying subjects with pathological dynamic PSV with accuracy higher than 80%. Furthermore, our preliminary data suggest that the same examination could identify diabetic subjects with ICFR with an accuracy of 80%.

Published
2008

Catalog

Books, media, physical & digital resources
See catalog results