Author: "Céline Pebrel‐Richard" / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

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1. Is an association of acro-osteolysis, bone fragility, and enchondromatosis a newfound disease caused by an amplification of PTHLH? A case report

Author: Stéphane Echaubard, Céline Pebrel-Richard, Aurélie Chausset, Jean-Louis Kemeny, Etienne Merlin, and Fanny Laffargue
Subjects: Radiography, Cross-Sectional Studies, Acro-Osteolysis, Adolescent, Rheumatology, Pediatrics, Perinatology and Child Health, Parathyroid Hormone-Related Protein, Humans, Immunology and Allergy, Female, Enchondromatosis, Child
Abstract: Background Acro-osteolysis (AO) refers to resorption of the distal finger and toe phalanges. It displays two patterns: (i) diffuse AO and (ii) transverse or bandlike AO. AO can be a sign of local distress (e.g. of toxic origin), but is very often a sign of a constitutional or systemic acquired disorder. Case presentation A 15-year-old girl was referred to a paediatric rheumatologist for recurrent pain in her fingertips. She presented a particular cross-sectional AO associated with the presence of intraosseous cysts and bone fragility with atypical fractures. Initial laboratory tests and radiological examination did not allow an etiological diagnosis. Genetic studies revealed a 12p11.22-p11.23 microduplication of 900 kb including the PTHLH (parathyroid hormone-like hormone) gene, which encodes for a hormone involved in the regulation of endochondral ossification and differentiation of chondrocytes, via its PTHLH receptor. Conclusions To date, 12p11.22-p11.23 duplications have been reported in five families with skeletal abnormalities, and in particular AO and enchondromatosis associated with bone fragility. This new observation, added to the other reported cases, suggests a close relationship between the presence of this microduplication and the skeletal abnormalities found in the patient. We suggest the descriptive name ABES (acro-osteolysis, bone fragility and enchondromatosis syndrome) to designate this disorder.
Published: 2022
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2. Hemizygous FGG p.Ala108Gly in a hypofibrinogenemic patient with a heterozygous 14.8 Mb deletion encompassing the entire fibrinogen gene cluster

Author: Alexander Couzens, Aurélien Lebreton, Frédéric Masclaux, Michel Guipponi, Céline Pebrel‐Richard, Fanny Laffargue, Piotr Gembara, Alessandro Casini, and Marguerite Neerman‐Arbez
Subjects: Heterozygote, Fibrinogens, Abnormal, Multigene Family, Fibrinogen, Humans, Hematology, General Medicine, Afibrinogenemia, Genetics (clinical)
Published: 2022
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3. Neurodevelopmental phenotype in 36 new patients with 8p inverted duplication-deletion: Genotype-phenotype correlation for anomalies of the corpus callosum

Author: Roseline Vibert, Cyril Mignot, Boris Keren, Sandra Chantot‐Bastaraud, Marie‐France Portnoï, Marie‐Christine Nouguès, Marie‐Laure Moutard, Anne Faudet, Sandra Whalen, Damien Haye, Catherine Garel, Nicolas Chatron, Massimiliano Rossi, Catherine Vincent‐Delorme, Odile Boute, Bruno Delobel, Joris Andrieux, Françoise Devillard, Charles Coutton, Jacques Puechberty, Céline Pebrel‐Richard, Cindy Colson, Marion Gerard, Chantal Missirian, Sabine Sigaudy, Tiffany Busa, Martine Doco‐Fenzy, Valérie Malan, Marlène Rio, Bérénice Doray, Damien Sanlaville, Jean‐Pierre Siffroi, Delphine Héron, Solveig Heide, Service de Génétique médicale [CHU Pitié-Salpêtrière], 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 de référence Déficiences Intellectuelles de Causes Rares [CHU Pitié-Salpétrière], UF de Génétique chromosomique [CHU Trousseau], CHU Trousseau [APHP], Service de Neuropédiatrie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Radiologie [CHU Trousseau], 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), Hôpital Jeanne de Flandre [Lille], Institut Catholique de Lille (ICL), Université catholique de Lille (UCL), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Génétique Clinique [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), Laboratoire de Génétique Moléculaire [Hôpital de la Timone - APHM], Département de génétique médicale [Hôpital de la Timone - APHM], 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)-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), 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 Hospitalier Universitaire de Reims (CHU Reims), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Génétique [CHU La Réunion], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], UF de Génétique moléculaire [CHU Trousseau], Couvet, Sandrine, and Maladies génétiques d'expression pédiatrique (U933)
Subjects: MESH: Chromosome Deletion, [SDV]Life Sciences [q-bio], AnCC, Trisomy, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, MESH: Corpus Callosum, MESH: Leukoencephalopathies, MESH: Phenotype, MESH: Intellectual Disability, Corpus Callosum, 8p inverted duplication-deletion, Leukoencephalopathies, Intellectual Disability, Genetics, anomalies of the corpus callosum, Humans, intellectual disability (ID), Genetics (clinical), Genetic Association Studies, MESH: Genetic Association Studies, MESH: Humans, MESH: Chromosome Inversion, [SDV] Life Sciences [q-bio], Phenotype, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Chromosome Inversion, MESH: Trisomy, Chromosome Deletion, candidate genes, MESH: Chromosomes, Human, Pair 8, invdupdel(8p), Chromosomes, Human, Pair 8
Abstract: International audience; Inverted duplication deletion 8p [invdupdel(8p)] is a complex and rare chromosomal rearrangement that combines a distal deletion and an inverted interstitial duplication of the short arm of chromosome 8. Carrier patients usually have developmental delay and intellectual disability (ID), associated with various cerebral and extra-cerebral malformations. Invdupdel(8p) is the most common recurrent chromosomal rearrangement in ID patients with anomalies of the corpus callosum (AnCC). Only a minority of invdupdel(8p) cases reported in the literature to date had both brain cerebral imaging and chromosomal microarray (CMA) with precise breakpoints of the rearrangements, making genotype-phenotype correlation studies for AnCC difficult. In this study, we report the clinical, radiological, and molecular data from 36 new invdupdel(8p) cases including three fetuses and five individuals from the same family, with breakpoints characterized by CMA. Among those, 97% (n = 32/33) of patients presented with mild to severe developmental delay/ID and 34% had seizures with mean age of onset of 3.9 years (2 months-9 years). Moreover, out of the 24 patients with brain MRI and 3 fetuses with neuropathology analysis, 63% (n = 17/27) had AnCC. We review additional data from 99 previously published patients with invdupdel(8p) and compare data of 17 patients from the literature with both CMA analysis and brain imaging to refine genotype-phenotype correlations for AnCC. This led us to refine a region of 5.1 Mb common to duplications of patients with AnCC and discuss potential candidate genes within this region.
Published: 2021
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4. Optical genome mapping enables constitutional chromosomal aberration detection

Author: Ronald van Beek, Caroline Schluth-Bolard, Jean Michel Dupont, Tuomo Mantere, Michiel Oorsprong, Alexander Hoischen, Marc Pauper, Dominique Smeets, Kornelia Neveling, Laila El Khattabi, Céline Pebrel-Richard, Marion Benoist, Marian Stevens-Kroef, Aziza Lebbar, Tony Yammine, Imane Baatout, Faten Hsoumi, Guillaume van der Zande, Damien Sanlaville, Ellen Kater-Baats, Daniel Olde-Weghuis, Wed Majdali, and Susan Vermeulen
Subjects: medicine.medical_specialty, DNA Copy Number Variations, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], Ring chromosome, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Chromosome Disorders, Computational biology, Biology, Article, All institutes and research themes of the Radboud University Medical Center, Gene mapping, Genetics, medicine, Humans, Copy-number variation, Genetics (clinical), Chromosome Aberrations, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Genome, Human, Breakpoint, Other Research Radboud Institute for Health Sciences [Radboudumc 0], Cytogenetics, Chromosome Mapping, Karyotype, Microarray Analysis, Karyotyping, Cytogenetic Analysis, Human genome, DNA microarray
Abstract: Chromosomal aberrations including structural variations (SVs) are a major cause of human genetic diseases. Their detection in clinical routine still relies on standard cytogenetics. Drawbacks of these tests are a very low resolution (karyotyping) and the inability to detect balanced SVs or indicate the genomic localization and orientation of duplicated segments or insertions (copy number variant [CNV] microarrays). Here, we investigated the ability of optical genome mapping (OGM) to detect known constitutional chromosomal aberrations. Ultra-high-molecular-weight DNA was isolated from 85 blood or cultured cells and processed via OGM. A de novo genome assembly was performed followed by structural variant and CNV calling and annotation, and results were compared to known aberrations from standard-of-care tests (karyotype, FISH, and/or CNV microarray). In total, we analyzed 99 chromosomal aberrations, including seven aneuploidies, 19 deletions, 20 duplications, 34 translocations, six inversions, two insertions, six isochromosomes, one ring chromosome, and four complex rearrangements. Several of these variants encompass complex regions of the human genome involved in repeat-mediated microdeletion/microduplication syndromes. High-resolution OGM reached 100% concordance compared to standard assays for all aberrations with non-centromeric breakpoints. This proof-of-principle study demonstrates the ability of OGM to detect nearly all types of chromosomal aberrations. We also suggest suited filtering strategies to prioritize clinically relevant aberrations and discuss future improvements. These results highlight the potential for OGM to provide a cost-effective and easy-to-use alternative that would allow comprehensive detection of chromosomal aberrations and structural variants, which could give rise to an era of "next-generation cytogenetics."
Published: 2021

5. Analysis of the cost effectiveness of different strategies for the antenatal diagnosis of chromosomal aberrations in cases of ultrasound-identified fetal abnormalities

Author: Laurent Gerbaud, Laetitia Gouas, Charline Mourgues, Anne Debost-Legrand, Philippe Vago, Céline Pebrel-Richard, Carole Goumy, Eleonore Eymard-Pierre, H. Laurichesse-Delmas, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, medicine.medical_specialty, Cost effectiveness, [SDV]Life Sciences [q-bio], Cost-Benefit Analysis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Ultrasonography, Prenatal, Single test, Prenatal ultrasound, Fetus, Direct test, Predictive Value of Tests, Pregnancy, Prenatal Diagnosis, medicine, Humans, Positive test, health care economics and organizations, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Chromosome Aberrations, business.industry, Obstetrics, Ultrasound, Decision Trees, General Medicine, humanities, 3. Good health, Fetal Diseases, Karyotyping, Cytogenetic Analysis, Female, France, business, Algorithms, Cytogenetic Techniques
Abstract: Objective Principal objective of this work was to analyse the cost effectiveness of different sequences of cytogenetic techniques from the hospital's point of view, after prenatal ultrasound has identified fetal malformations. Methods Cytogenetic tests were performed for each case in 3 strategies, and their results are reported and compared to one reference strategy. Two new simulated strategies were considered: chromosomal microarrays alone and a direct test + CMA. Main outcomes measures cost-effectiveness ratio. Results A single test result was positive in 234 of the 835 pregnancies studied (28%). CMA alone would have identified 239 abnormalities. In the simulated direct test + CMA sequence, the direct test alone would have been positive for 66.1% of the abnormalities identified. When testing was indicated for NT, reference strategy (Direct + karyotyping) costs 1 084.8 euros by positive test results. Strategies Direct + CMA and CMA alone cost respectively 992.7 and 550.0 euros by positive test results. For OUM indications, reference strategy costs 2 937.8 euros by positive test results. Strategies Direct + CMA and CMA alone cost respectively, 2 118.4 and 1 304.7 euros by positive test results. Conclusions CMA appears to be the most effective test for prenatal cytogenetic diagnosis of fetal abnormalities identified by ultrasound.
Published: 2020
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6. Further refining the critical region of 10q26 microdeletion syndrome: A possible involvement of INSYN2 and NPS in the cognitive phenotype

Author: Christine Francannet, Céline Pebrel-Richard, Amélie Delabaere, Laetitia Gouas, Mathis Lepage, Andrei Tchirkov, Florian Cherik, Philippe Vago, Ganaelle Remerand, Carole Goumy, Gaelle Salaun, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)
Subjects: Adult, Male, Proband, Candidate gene, medicine.medical_specialty, Microcephaly, [SDV]Life Sciences [q-bio], Short stature, 03 medical and health sciences, Cognition, 0302 clinical medicine, Intellectual disability, Genetics, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Psychomotor retardation, Chromosomes, Human, Pair 10, Learning Disabilities, business.industry, Neuropeptides, Facies, Infant, General Medicine, Microdeletion syndrome, medicine.disease, Dermatology, rac GTP-Binding Proteins, Phenotype, medicine.anatomical_structure, Forehead, Female, Chromosome Deletion, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Background The 10q26 subtelomeric microdeletion syndrome is a rare and clinically heterogeneous disorder. The precise relationships between the causative genes and the phenotype are unclear. Case presentation We report two new cases of 860 kb deletion of 10q26.2 identified by array CGH in a fetus with intrauterine growth retardation and his mother. The deleted region encompassed only four coding genes, DOCK1, INSYN2, NPS and FOX12. The proband had dysmorphic facies characterized by a high forehead, malformed ears, a prominent nose, and retrognathia. He had bilateral club feet, clinodactily and mild psychomotor retardation. His mother had a short stature, microcephaly, a long face with a high forehead and bitemporal narrowing, arched and sparse eyebrows, strabismus, prominent nose and chin, a thin upper lip and large protruding ears, and mild intellectual disability. Conclusions This study presents the smallest 10q26.2 deletion so far identified, which further refines the minimal critical region associated with the 10q26 microdeletion syndrome. It focuses on three genes potentially responsible for the phenotype: DOCK1, which is the major candidate gene, and INSYN2 and NPS, which could be involved in cognitive functions.
Published: 2021
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7. Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with developmental disorders

Author: Brigitte Gilbert-Dussardier, Patrick Edery, Flavie Diguet, Géraldine Joly-Hélas, Fanny Morice-Picard, Nicolas Chatron, Jeanne Amiel, Fabienne Prieur, Jérome Toutain, Sandra Whalen, Marine Lebrun, Gwenaël Nadeau, Sylvie Jaillard, Céline Pebrel-Richard, Annabelle Chaussenot, Bénédicte Demeer, Florence Demurger, Sophie Dupuis-Girod, Marianne Till, Nicole Philip, Jacques Puechberty, Laurent Pasquier, Pierre-Antoine Rollat-Farnier, Claire Bardel, Anne-Marie Guerrot, Anne-Claude Tabet, Sylvie Odent, Annick Toutain, Alain Verloes, Jean-Michel Dupont, Christine Coubes, Aziza Lebbar, Yline Capri, Bertrand Isidor, James Lespinasse, Didier Lacombe, Julie Masson, Sophie Blesson, Marine Houlier, Véronique Paquis-Flucklinger, Michèle Mathieu-Dramard, Florence Amblard, Patrick Callier, Jonathan Levy, Chantal Missirian, Véronique Satre, Marie-France Portnoï, Cyril Mignot, Stéphanie Valence, Catherine Sarret, Sébastien Moutton, Françoise Devillard, Alice Masurel-Paulet, Caroline Schluth-Bolard, Patrick Collignon, Jean-Pierre Siffroi, Marie-Pierre Cordier, Renaud Touraine, Marlène Rio, Céline Dupont, Cédric Le Caignec, Damien Sanlaville, Audrey Putoux, Morgane Plutino, Valérie Kremer, Valérie Malan, Martine Doco-Fenzy, Alexandra Afenjar, Caroline Rooryck-Thambo, Massimiliano Rossi, Linda Pons, Gaetan Lesca, Laurence Faivre, Laboratoire de Biologie Moléculaire de la Cellule (LBMC), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Service de Génétique [CHU Lyon] (Centre de pathologie de l'Est), Hospices civils de Lyon (HCL), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de génétique et procréation, Université Joseph Fourier - Grenoble 1 (UJF)-Hôpital Couple-Enfant, 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), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), 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), Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Service de Génétique Médicale, Centre Hospitalier Intercommunal, Toulon, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de génétique médicale, CHU Amiens-Picardie, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Génétique médicale [Centre Hospitalier de Vannes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Pôle Couple-Enfant, Département de Génétique et Procréation, Centre de génétique et Centre de référence maladies rares et anomalies du développement et syndromes malformatifs du Centre Est, Département de Génétique et Procréation UF-Hôpital Couple Enfant de Grenoble-CHU Grenoble, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Service de Génétique, Hospices Civils de Lyon (HCL)-Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Groupe Hospitalier Est, Génétique Médicale, Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre de Référence Anomalies du Développement Ouest, CHU Rouen, Normandie Université (NU), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Service de génétique [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Université de Bordeaux (UB), Service de Génétique Clinique Chromosomique et Moléculaire, CHU Saint-Etienne, Université de Lyon, Département de Génétique Chromosomique, Bâtiment Hôtel Dieu - Centre Hospitalier de Chambéry, École normale supérieure - Rennes (ENS Rennes), Laboratoire Histologie Embryologie Cytogénétique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Département de génétique médicale [Hôpital de la Timone - APHM], 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), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Cytogénétique, Centre hospitalier de Valence, CHU Clermont-Ferrand, 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 Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Dept of Immunology, Genetics and Pathology, Service de Génétique Clinique (CHU de Saint-Etienne), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de néphrologie pédiatrique [CHU Necker], CHU Bordeaux [Bordeaux], Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de génétique et embryologie médicales [CHU Trousseau], 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 cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, Service de génétique, CHU Saint-Etienne-Hôpital nord, Service de génétique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Physiopathologie et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), French National Agency for Research, French Ministry of Health, École normale supérieure de Lyon (ENS de Lyon)-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 d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), 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 ), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], 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 (CRNL), Université Nice Sophia Antipolis (... - 2019) (UNS), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), 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), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: Adult, Male, 0301 basic medicine, Candidate gene, Adolescent, DNA Copy Number Variations, Developmental Disabilities, 030105 genetics & heredity, Genome, Translocation, Genetic, Structural variation, Chromosome Breakpoints, Structure-Activity Relationship, Young Adult, 03 medical and health sciences, symbols.namesake, position effect, Genetics, Humans, Child, Gene, Genetic Association Studies, Genetics (clinical), Paired-end tag, ComputingMilieux_MISCELLANEOUS, chromosomal rearrangements, Chromosome Aberrations, Gene Rearrangement, Whole genome sequencing, Sanger sequencing, whole genome sequencing, biology, structural variation, Infant, NFIX, Phenotype, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, intellectual disability, Child, Preschool, biology.protein, symbols, Female, Biomarkers
Abstract: BackgroundBalanced chromosomal rearrangements associated with abnormal phenotype are rare events, but may be challenging for genetic counselling, since molecular characterisation of breakpoints is not performed routinely. We used next-generation sequencing to characterise breakpoints of balanced chromosomal rearrangements at the molecular level in patients with intellectual disability and/or congenital anomalies.MethodsBreakpoints were characterised by a paired-end low depth whole genome sequencing (WGS) strategy and validated by Sanger sequencing. Expression study of disrupted and neighbouring genes was performed by RT-qPCR from blood or lymphoblastoid cell line RNA.ResultsAmong the 55 patients included (41 reciprocal translocations, 4 inversions, 2 insertions and 8 complex chromosomal rearrangements), we were able to detect 89% of chromosomal rearrangements (49/55). Molecular signatures at the breakpoints suggested that DNA breaks arose randomly and that there was no major influence of repeated elements. Non-homologous end-joining appeared as the main mechanism of repair (55% of rearrangements). A diagnosis could be established in 22/49 patients (44.8%), 15 by gene disruption (KANSL1, FOXP1, SPRED1, TLK2, MBD5, DMD, AUTS2, MEIS2, MEF2C, NRXN1, NFIX, SYNGAP1, GHR, ZMIZ1) and 7 by position effect (DLX5, MEF2C, BCL11B, SATB2, ZMIZ1). In addition, 16 new candidate genes were identified. Systematic gene expression studies further supported these results. We also showed the contribution of topologically associated domain maps to WGS data interpretation.ConclusionPaired-end WGS is a valid strategy and may be used for structural variation characterisation in a clinical setting.
Published: 2019
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8. Spatial organization of chromosome territories in the interphase nucleus of trisomy 21 cells

Author: Natasha Ollier, Céline Pebrel-Richard, Bruno Pereira, Stephan Kemeny, Gaelle Salaun, Eugenie Maurin, Carole Goumy, Christophe Tatout, Laetitia Gouas, Philippe Vago, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])
Subjects: 0301 basic medicine, Trisomy 21, Primary Cell Culture, Nuclear architecture, Chromosomal translocation, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Translocation, Genetic, 03 medical and health sciences, Pregnancy, Genetics, medicine, Humans, Radial arrangement, Supernumerary, Lymphocytes, Interphase, Genetics (clinical), Spatial organization, In Situ Hybridization, Fluorescence, 3D-FISH, Cell Nucleus, Chromosome, Fibroblasts, medicine.disease, Aneuploidy, Chromatin, Cell biology, 030104 developmental biology, Chromosome Territory, Karyotyping, Chromosome territory, Amniocentesis, Female, Chorionic Villi, Down Syndrome, Trisomy, Chromosome 21, Developmental biology
Abstract: International audience; In the interphase cell nucleus, chromosomes adopt a conserved and non-random arrangement in subnuclear domains called chromosome territories (CTs). Whereas chromosome translocation can affect CT organization in tumor cell nuclei, little is known about how aneuploidies can impact CT organization. Here, we performed 3D-FISH on control and trisomic 21 nuclei to track the patterning of chromosome territories, focusing on the radial distribution of trisomic HSA21 as well as 11 disomic chromosomes. We have established an experimental design based on cultured chorionic villus cells which keep their original mesenchymal features including a characteristic ellipsoid nuclear morphology and a radial CT distribution that correlates with chromosome size. Our study suggests that in trisomy 21 nuclei, the extra HSA21 induces a shift of HSA1 and HSA3 CTs out toward a more peripheral position in nuclear space and a higher compaction of HSA1 and HSA17 CTs. We posit that the presence of a supernumerary chromosome 21 alters chromosome compaction and results in displacement of other chromosome territories from their usual nuclear position.
Published: 2018
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9. Is BRCA2 involved in early onset colorectal cancer risk?

Author: Yves-Jean Bignon, Nancy Uhrhammer, Sandrine Viala, Mathias Cavaillé, Michael Rodrigues, Carole Corsini, Sandrine M. Caputo, Nicolas Barnich, Mathilde Gay-Bellile, Maud Privat, Céline Pebrel-Richard, Yannick Bidet, Alexandra Martins, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Génétique du cancer et des maladies neuropsychiatriques (GMFC), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire d'automatique et de génie des procédés (LAGEP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Centre National de la Recherche Scientifique (CNRS), and OUERTANI, jeannette
Subjects: 0301 basic medicine, Adult, Male, Colorectal cancer, Pcr cloning, 030105 genetics & heredity, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 03 medical and health sciences, Exon, symbols.namesake, Genetics, medicine, Humans, Genetic Predisposition to Disease, Letters to the Editor, Letter to the Editor, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Genetic Association Studies, Early onset, Sanger sequencing, BRCA2 Protein, Cancer, RNA, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Exons, medicine.disease, Molecular biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Pedigree, Alternative Splicing, 030104 developmental biology, Genetic marker, Mutation, symbols, Female, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Colorectal Neoplasms
Abstract: A, Closed symbols indicate patients affected with cancer. Open symbols indicate healthy individuals. The type of cancer and age at presentation are given in brackets. Blue circle represents c.4471_4474del variant and red circle represents the c.9648 + 1G > A. B, RNA was extracted from blood of patient III-3 and his sisters III-1 and III-4. RT-PCR analysis was performed with primers mapping to exons 25 and 27, and PCR products were separated by Bioanalyzer electrophoresis. The sizes of the DNA marker (M) are indicated to the left. LM, lower marker; UM, upper marker. C, Each RT-PCR product from patient III-3 was gel-purified and analyzed by Sanger sequencing. The 297-bp band corresponds to the reference BRCA2 transcript and the 150-bp band corresponds to a BRCA2 transcript lacking exon 26.
Published: 2019
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10. A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

Author: François Vialard, Eva Pipiras, Pascale Kleinfinger, Dominique Martin-Coignard, Marie Catty, Elisabeth Flori, Emilie Landais, Mylène Valduga, Marie-France Portnoï, Aline Receveur, Agnès Choiset, Ghislaine Plessis, Nathalie Le Meur, Audrey Basinko, Justine Besseau-Ayasse, James Lespinasse, Radu Harbuz, Céline Poirsier, Martine Doco-Fenzy, Pascaline Letard, Caroline Schluth-Bolard, Anne Bazin, Jérôme Toutain, Fabienne Prieur, Florence Amblard, Cédric Le Caignec, Tiffany Busa, Marie Christine de Blois, Melanie Jimenez, Patrick Callier, Chantal Missirian, Céline Pebrel-Richard, Paul Kuentz, Catherine Yardin, François Cartault, Hakima Lallaoui, Service de génétique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), UVSQ - Département de maïeutique (UVSQ Maïeutique), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), 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), CHU Bordeaux [Bordeaux], Département de génétique médicale [Hôpital de la Timone - APHM], 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), 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 hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Génétique [CHU Caen], 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), Normandie Université (NU), Génétique moléculaire et génétique épidémiologique, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de cytogénétique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], 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), Laboratoire de cytogénétique et génétique moléculaire [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), Service de génétique, Centre hospitalier Félix Guyon, Bellepierre, Département de Génétique Chromosomique, Bâtiment Hôtel Dieu - Centre Hospitalier de Chambéry, Laboratoire de génétique médicale et cytogénétique [Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), CHU Clermont-Ferrand, Service de Génétique et d'Embryologie Médicales [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Service d'histologie, embryologie et cytogénétique [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine Béclère, Département de génétique et procréation, Université Joseph Fourier - Grenoble 1 (UJF)-Hôpital Couple-Enfant, Service d'Histologie, cytologie, cytogénétique, biologie cellulaire [CHU Limoges], CHU Limoges, Activité Motrice et Adaptation PsychoPhysiologique (AMAPP), Université d'Orléans (UO), Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Service Histologie-embryologie-cytogénétique, Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Laboratoire Pasteur Cerba, Laboratoire de Cytogénétique, CHI Poissy-Saint-Germain, Service de gynécologie et obstétrique [CHI Poissy-Saint Germain], Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), 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), Institut Pasteur [Paris] (IP)-Laboratoire CERBA [Saint Ouen l'Aumône], 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Association des Cytogénéticiens de Langue Française, Gamètes, implantation, gestation (GIG), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Institut Pasteur [Paris]-Laboratoire CERBA [Saint Ouen l'Aumône], Service de génétique et embryologie médicales [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [Bondy]
Subjects: Adult, Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, 22q11 Deletion Syndrome, Adolescent, [SDV]Life Sciences [q-bio], Population, Article, 03 medical and health sciences, Intellectual disability, Genetics, medicine, Humans, Genetic Testing, Child, education, ComputingMilieux_MISCELLANEOUS, In Situ Hybridization, Fluorescence, Genetics (clinical), Comparative Genomic Hybridization, Fetus, education.field_of_study, business.industry, Incidence (epidemiology), Infant, Newborn, Cytogenetics, Infant, Microdeletion syndrome, medicine.disease, 3. Good health, 030104 developmental biology, Child, Preschool, Cohort, Paternal Inheritance, Female, France, business, Comparative genomic hybridization
Abstract: Although 22q11.2 deletion syndrome (22q11.2DS) is the most recurrent human microdeletion syndrome associated with a highly variable phenotype, little is known about the condition's true incidence and the phenotype at diagnosis. We performed a multicenter, retrospective analysis of postnatally diagnosed patients recruited by members of the Association des Cytogénéticiens de Langue Française (the French-Speaking Cytogeneticists Association). Clinical and cytogenetic data on 749 cases diagnosed between 1995 and 2013 were collected by 31 French cytogenetics laboratories. The most frequent reasons for referral of postnatally diagnosed cases were a congenital heart defect (CHD, 48.6%), facial dysmorphism (49.7%) and developmental delay (40.7%). Since 2007 (the year in which array comparative genomic hybridization (aCGH) was introduced for the routine screening of patients with intellectual disability), almost all cases have been diagnosed using FISH (96.1%). Only 15 cases (all with an atypical phenotype) were diagnosed with aCGH; the deletion size ranged from 745 to 2904 kb. The deletion was inherited in 15.0% of cases and was of maternal origin in 85.5% of the latter. This is the largest yet documented cohort of patients with 22q11.2DS (the most commonly diagnosed microdeletion) from the same population. French cytogenetics laboratories diagnosed at least 108 affected patients (including fetuses) per year from among a national population of ∼66 million. As observed for prenatal diagnoses, CHDs were the most frequently detected malformation in postnatal diagnoses. The most common CHD in postnatal diagnoses was an isolated septal defect.
Published: 2015
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11. Sperm meiotic segregation of a balanced interchromosomal reciprocal insertion resulting in recurrent spontaneous miscarriage

Author: Philippe Vago, Christine Francannet, Laetitia Gouas, Gaelle Salaun, Hanae Pons, Eleonore Eymard-Pierre, Céline Pebrel-Richard, Florence Brugnon, Carole Goumy, Andrei Tchirkov, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Clermont-Ferrand, Cytogénétique Médicale, Unité de Génétique Médicale, Hôtel-Dieu-CHU Clermont-Ferrand, Service de Cytogénétique Médicale [CHU Clermont-Ferrand], Centre d'Assistance Médicale à la Procréation [CHU Clermont-Ferrand] (AMP CECOS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)
Subjects: 0301 basic medicine, Proband, Adult, Male, Abortion, Habitual, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Translocation, Genetic, Andrology, 03 medical and health sciences, 0302 clinical medicine, Meiosis, Pregnancy, Chromosome Segregation, medicine, Humans, Gene, [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS, In Situ Hybridization, Fluorescence, Fetus, 030219 obstetrics & reproductive medicine, Spontaneous miscarriage, urogenital system, [SDV.BA]Life Sciences [q-bio]/Animal biology, Obstetrics and Gynecology, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Sperm, Spermatozoa, Semen Analysis, 030104 developmental biology, Reproductive Medicine, Female, Female partner, Developmental Biology
Abstract: Research question Is sperm fluorescence in-situ hybridization (FISH) useful to evaluate the risk of chromosomally unbalanced gametes in interchromosomal reciprocal insertion (IRI) carriers? How do these imbalances lead to recurrent miscarriages? Design This study reports a clinical and molecular study of a rare familial balanced IRI resulting in recurrent spontaneous miscarriage. Sperm FISH was performed to estimate the number of unbalanced gametes. Results A 31-year-old healthy male (proband) and his 28-year-old female partner were referred to the Genetics Department for three spontaneous miscarriages occurring during the first trimester of pregnancy. FISH analysis of the proband with the LSI TRA/D (14q11.2) and DiGeorge N25 (22q11.2) break-apart probes showed the presence of a balanced IRI between 14q11.2 and 22q11.2 chromosomal regions. This IRI was also identified in the proband's father. Sperm FISH with the same probes showed that more than 40% of gametes of the proband were unbalanced for either 14q11.2 or 22q11.2, despite normal sperm parameters. FISH analysis of a product of conception indicated that unbalanced gametes result in a non-viable fetus. Conclusions This study shows the value of sperm FISH analysis in improving genetic reproductive advice for IRI carriers. Disruption of critical genes through this rearrangement and their consequent functional impairment could result in recurrent miscarriages. In this case, several genes located in the 14q11.2 region, particularly RNase 3, would be good candidates to explain the lethality of the imbalances.
Published: 2017
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12. Congenital diaphragmatic hernia may be associated with 17q12 microdeletion syndrome

Author: Christine Francannet, Denis Gallot, Fanny Laffargue, Laetiti Gouas, Eleonore Eymard-Pierre, Carole Goumy, Mathilde Gay-Bellile, Andrei Tchirkov, Philippe Vago, Stéphen Kemeny, and Céline Pebrel-Richard
Subjects: medicine.medical_specialty, Candidate gene, Pathology, Disease, Internal medicine, Diabetes mellitus, Genetics, medicine, Humans, Cognitive impairment, Genetics (clinical), Comparative Genomic Hybridization, business.industry, Infant, Newborn, Facies, Infant, Congenital diaphragmatic hernia, Syndrome, Microdeletion syndrome, medicine.disease, Phenotype, Diaphragm (structural system), Endocrinology, Child, Preschool, Chromosome Deletion, Hernias, Diaphragmatic, Congenital, business, Chromosomes, Human, Pair 17
Abstract: Microdeletions of 17q12 encompassing TCF2 are associated with maturity-onset of diabetes of the young type 5, cystic renal disease, pancreatic atrophy, Mullerian aplasia in females and variable cognitive impairment. We report on a patient with a de novo 17q12 microdeletion, 1.8 Mb in size, associated with congenital diaphragmatic hernia (CDH). The 5-year-old male patient presented multicystic renal dysplasia kidneys, minor facial dysmorphic features and skeletal anomalies, but neither developmental delay nor behavioral abnormalities. CDH has been previously associated with the 17q12 microdeletion syndrome only in one prenatal case. The present study reinforces the hypothesis that CDH is part of the phenotype for 17q12 microdeletion and that 17q12 encompasses candidate(s) gene(s) involved in diaphragm development. We suggest that PIGW, a gene involved in an early step of GPI biosynthesis, could be a strong candidate gene for CDH. © 2014 Wiley Periodicals, Inc.
Published: 2014
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13. Clinical and molecular description of a 17q21.33 microduplication in a girl with severe kyphoscoliosis and developmental delay

Author: Mathilde Gay-Bellile, Christine Francannet, Andrei Tchirkov, Stephan Kemeny, Céline Pebrel-Richard, Carole Goumy, Eleonore Eymard-Pierre, Laetitia Gouas, and Philippe Vago
Subjects: Microcephaly, Adolescent, Developmental Disabilities, Genetic counseling, Locus (genetics), Biology, Bioinformatics, Collagen Type I, Gene Duplication, Intellectual Disability, Protein Phosphatase 1, Sarcoglycans, Genetics, medicine, Humans, Copy-number variation, Genetics (clinical), Segmental duplication, SGCA, Comparative Genomic Hybridization, Extracellular Matrix Proteins, General Medicine, medicine.disease, Musculoskeletal Abnormalities, Collagen Type I, alpha 1 Chain, Chromosome 17 (human), Scoliosis, Female, Chromosomes, Human, Pair 17, Comparative genomic hybridization
Abstract: High proportion of disease-associated copy number variant maps to chromosome 17. Genomic studies have provided an insight into its complex genomic structure such as relative abundance of segmental duplication and intercepted repetitive elements. 17q21.31, 17q11.2 and 17q12 loci are well known on this chromosome and are associated with microdeletion and microduplication syndrome. No syndrome associated with 17q21.33 locus have been described. We report clinical, cytogenetic and molecular investigations of a 13 years-old girl admitted for evaluation of microcephaly, scoliosis, skeletal defects and learning difficulties. We carried out detailed analysis of the clinical phenotype of this patient and investigated the genetic basis using Agilent 180K Array Comparative Genomic Hybridization. We identified a ∼0.9 Mb de novo microduplication on chromosome 17q21.33. Four genes, COL1A1, SGCA, PPP1R9B and CHAD located within the duplicated region are possible candidates for clinical features present in our patients. Gene expression studies by real-time RT-PCR assay only showed an overexpression of SGCA (P < 0.01), a component of the dystrophin glycoprotein complex. Defect of SGCA was previously shown to lead to severe childhood autosomal recessive muscular dystrophy (LGMD2D) which result in progressive muscle weakness and can also be associated with hyperlordosis or scoliosis. Further cases with similar duplications are expected to be diagnosed. This will contribute to the delineation of this potential new microduplication syndrome and to improve genetic counseling.
Published: 2014
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14. Impaired Presynaptic High-Affinity Choline Transporter Causes a Congenital Myasthenic Syndrome with Episodic Apnea

Author: Seana O'Regan, Tiziana Mongini, Céline Buon, Anne Marie Beaufrere, Yoshiteru Azuma, Bertrand Fontaine, Hanns Lochmüller, S. Bauche, Ana Töpf, Chiara Fiorillo, Jean-François Deleuze, E. Lacène, Julien Thevenon, Gisèle Bonne, Damien Sternberg, C. Burloiu, Yannis Duffourd, Isabelle Desguerre, Isabelle Nelson, Guy Brochier, Anne Boland, Benoit Bœuf, Michèle Mayer, Laure Strochlic, Jocelyn Laporte, Laurence Faivre, Sophie Nicole, Ganaelle Remerand, Céline Pebrel-Richard, Laurent Servais, Federica Ricci, Guja Astrea, Doris Lechner, Salima El Chehadeh-Djebbar, Nassima Bouzidi, Fanny Laffargue, Bruno Eymard, Marie Christine Nougues, Norma B. Romero, Grace McMacken, Carmen Sandu, Niculina Butoianu, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Newcastle University [Newcastle], Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-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 Clermont-Ferrand, Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Université Bourgogne Franche-Comté [COMUE] (UBFC), FHU TRANSLAD, Département de Génétique, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), FHU TRANSLAD (CHU de Dijon), Università degli studi di Torino = University of Turin (UNITO), Università degli studi di Genova = University of Genoa (UniGe), 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)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Service de Génétique Médical, CHU Pitié-Salpêtrière [APHP], Unité de Morphologie Neuromusculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie moléculaire et cellulaire de la différenciation, Université Joseph Fourier - Grenoble 1 (UJF)-Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Thérapie des maladies du muscle strié, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de recherche en myologie, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Albert Einstein College of Medicine, Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de neurologie pédiatriques et maladies du dévéloppement, Service de neuropédiatrie [Trousseau], AFM-Telethon 20030Fondation Maladies Rares within the Myocapture sequencing project Medical Research Council UK G1002274 98482 European Union Seventh Framework Programme (FP7) 305444 305121, [ANR-10-IAIHU-06],« Investissements d'avenir » ,Agence nationale de la recherche (ANR), ANR-10-INBS-09-01/10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), 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), 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), Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Albert Einstein College of Medicine [New York], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), ANR-10-IAHU-0006,IHU-A-ICM,Institut de Neurosciences Translationnelles de Paris(2010), ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), 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], and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: 0301 basic medicine, Male, Apnea, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, receptors, respiratory rhythm, Compound heterozygosity, Synaptic Transmission, 0302 clinical medicine, Genetics(clinical), Exome, neurotransmission, Child, Genetics (clinical), Arthrogryposis, Muscle Weakness, Symporters, Homozygote, deficiency, Congenital myasthenic syndrome, Hypotonia, Cholinergic Neurons, 3. Good health, medicine.anatomical_structure, acetyltransferase, Child, Preschool, butyrylcholinesterase, Muscle Hypotonia, Female, medicine.symptom, medicine.medical_specialty, Heterozygote, Adolescent, Mutation, Missense, Neuromuscular Junction, Presynaptic Terminals, Genes, Recessive, Butyrylcholinesterase, HEK293 Cells, Humans, Infant, Infant, Newborn, Mutation, Myasthenia Gravis, Genetics, Neuromuscular junction, 03 medical and health sciences, neuromuscular-junction, Internal medicine, Report, expression, medicine, Recessive, Cholinergic neuron, Preschool, business.industry, Muscle weakness, Newborn, medicine.disease, mutations, Choline transporter, 030104 developmental biology, Endocrinology, Genes, Cholinergic, Missense, business, knockout mouse, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The neuromuscular junction (NMJ) is one of the best-studied cholinergic synapses. Inherited defects of peripheral neurotransmission result in congenital myasthenic syndromes (CMS5), a clinically and genetically heterogeneous group of rare diseases with fluctuating fatigable muscle weakness as the clinical hallmark. Whole-exome sequencing and Sanger sequencing in six unrelated families identified compound heterozygous and homozygous mutations in SLC5A7 encoding the presynaptic sodium-dependent high-affinity choline transporter 1 (CHT), which is known to be mutated in one dominant form of distal motor neuronopathy (DHMN7A). We identified 11 recessive mutations in SLC5A7 that were associated with a spectrum of severe muscle weakness ranging from a lethal antenatal form of arthrogryposis and severe hypotonia to a neonatal form of CMS with episodic apnea and a favorable prognosis when well managed at the clinical level. As expected given the critical role of CHT for multisystemic cholinergic neurotransmission, autonomic dysfunctions were reported in the antenatal form and cognitive impairment was noticed in half of the persons with the neonatal form. The missense mutations induced a near complete loss of function of CHT activity in cell models. At the human NMJ, a delay in synaptic maturation and an altered maintenance were observed in the antenatal and neonatal forms, respectively. Increased synaptic expression of butyrylcholinesterase was also observed, exposing the dysfunction of cholinergic metabolism when CHT is deficient in vivo. This work broadens the clinical spectrum of human diseases resulting from reduced CHT activity and highlights the complexity of cholinergic metabolism at the synapse.
Published: 2016
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15. A new case of 8q22.1 microdeletion restricts the critical region for Nablus mask-like facial syndrome

Author: Laetitia Gouas, Andrei Tchirkov, Philippe Vago, Anne Debost-Legrand, Michel Giollant, Eleonore Eymard-Pierre, Wiem Ayed, Christine Francannet, Carole Goumy, and Céline Pebrel-Richard
Subjects: Male, Microcephaly, Developmental Disabilities, Karyotype, Potential candidate, Blepharophimosis, Biology, Craniofacial Abnormalities, Nablus mask-like facial syndrome, Genetics, medicine, Humans, Abnormalities, Multiple, Global developmental delay, Autistic Disorder, In Situ Hybridization, Fluorescence, Genetics (clinical), Comparative Genomic Hybridization, Infant, Comparative Genome Hybridization, medicine.disease, Phenotype, I-kappa B Kinase, Autism, Chromosome Deletion, Chromosomes, Human, Pair 8
Abstract: Microdeletions of 8q21.3–8q22.1 have been identified in all patients with Nablus mask-like facial syndrome (NMLFS). A recent report of a patient without this specific phenotype presented a 1.6 Mb deletion in this region that partially overlapped with previously reported 8q21.3 microdeletions, thus restricting critical region for this syndrome. We report on another case of an 8q21.3 deletion revealed by array comparative genome hybridization (aCGH) in a 4-year-old child with global developmental delay, autism, microcephaly, but without Nablus phenotype. The size of the interstitial deletion was estimated to span 5.2 Mb. By combining the data from previous reports on 8q21.3–8q22.1 deletions and our case, we were able to narrow the critical region of Nablus syndrome to 0.5 Mb. The deleted region includes FAM92A1, which seems to be a potential candidate gene in NMLFS. © 2012 Wiley Periodicals, Inc.
Published: 2012
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16. An atypical 0.8 Mb inherited duplication of 22q11.2 associated with psychomotor impairment

Author: Nathalie Blanc, Eleonore Eymard-Pierre, Andrei Tchirkov, Christine Francannet, Laetitia Gouas, Stephan Kemeny, Carole Goumy, Philippe Vago, and Céline Pebrel-Richard
Subjects: Male, TBX1, Chromosomes, Human, Pair 22, Genetic counseling, Population, Biology, Chromosome Duplication, Gene duplication, DiGeorge Syndrome, Genetics, Humans, Abnormalities, Multiple, Multiplex ligation-dependent probe amplification, education, Genetics (clinical), Comparative Genomic Hybridization, education.field_of_study, General Medicine, Low copy repeats, Phenotype, Genetic Loci, Child, Preschool, Psychomotor Disorders, Multiplex Polymerase Chain Reaction, Comparative genomic hybridization
Abstract: Microduplications 22q11.2 have been recently characterized as a new genomic duplication syndrome showing an extremely variable phenotype ranging from normal or mild learning disability to multiple congenital defects and sharing some overlapping features with DiGeorge/velocardiofacial syndrome (DGS/VCFS), including heart defects, urogenital abnormalities and velopharyngeal insufficiency. We present an atypical and inherited 0.8-Mb duplication at 22q11.2, in the distal segment of the DGS/VCFS syndrome typically deleted region (TDR), in a 3-year-old boy with motor delay, language disorders and mild facial phenotype. This 22q11.2 microduplication was identified by MLPA, designed to detect recurrent microdeletions and microduplications of chromosomal regions frequently involved in mental retardation syndromes and was further characterized by aCGH. The duplicated region encompasses 14 genes, excluding TBX1 but including CRKL, ZNF74, PIK4CA, SNAP29 and PCQAP known to contribute to several aspects of the DGS/VCFS phenotype. To the best of our knowledge, only one case of an isolated duplication in the distal segment of the TDR between chromosome 22-specific low-copy repeats B (LCR22-B) and D (LCR22-D) has been published, but the present report is the first one with a detailed description of physical and developmental features in a patient carrying this kind of atypical 22q11.2 duplication. This case illustrates the importance of reporting unusual 22q11.2 duplications to further evaluate the incidence of these rearrangements in the general population and to improve genotype-phenotype correlations and genetic counseling.
Published: 2012
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17. Prenatal Screening of 21 Microdeletion/Microduplication Syndromes and Subtelomeric Imbalances by MLPA in Fetuses with Increased Nuchal Translucency and Normal Karyotype

Author: Laetitia Gouas, Eleonore Eymard-Pierre, Didier Lémery, H. Laurichesse-Delmas, Philippe Vago, Stephan Kemeny, Andrei Tchirkov, Céline Pebrel-Richard, Carole Goumy, and Anne-Marie Beaufrère
Subjects: Adult, medicine.medical_specialty, Adolescent, DNA Copy Number Variations, Karyotype, Chromosomal translocation, Prenatal diagnosis, Chromosome Disorders, Biology, Young Adult, Chromosome Duplication, Genetics, medicine, Humans, Multiplex ligation-dependent probe amplification, Molecular Biology, Increased nuchal translucency, Genetics (clinical), Fetus, Obstetrics, Subtelomere, Molecular Diagnostic Techniques, dup, Female, Chromosome Deletion, DNA Probes, Nuchal Translucency Measurement, Nucleic Acid Amplification Techniques
Abstract: Fetuses with increased nuchal translucency thickness (NT) are at increased risk for chromosomal abnormalities. In case of a normal karyotype, a minority of them may present with structural abnormalities or genetic syndromes, which may be related to submicroscopic chromosomal imbalances. The objective of this study was to evaluate whether MLPA screening of 21 syndromic and subtelomeric regions could improve the detection rate of small chromosomal aberrations in fetuses with increased NT and a normal karyotype. A total of 106 prenatal samples from fetuses with NT ≥99th centile and normal R- and G-banding were analyzed by MLPA for subtelomeric imbalances (SALSA P036 and P070) and 21 syndromic regions (SALSA P245). One sample showed a benign CNV (dup(8)pter, FBXO25 gene), and 1 patient was found to have a loss of 18qter and a gain of 5pter as a result of an unbalanced translocation. The incidence of cryptic pathogenic variants was
Published: 2015

18. De novo 2q36.1q36.3 interstitial deletion involving the PAX3 and EPHA4 genes in a fetus with spina bifida and cleft palate

Author: Carole, Goumy, Mathilde, Gay-Bellile, Eléonore, Eymard-Pierre, Stephan, Kemeny, Laetitia, Gouas, Pierre, Déchelotte, Denis, Gallot, Lauren, Véronèse, Andrei, Tchirkov, Céline, Pebrel-Richard, and Philippe, Vago
Subjects: Adult, Comparative Genomic Hybridization, Receptor, EphA4, Gene Expression Regulation, Developmental, Cleft Palate, Fetus, Pregnancy, Chromosomes, Human, Pair 2, Karyotyping, Prenatal Diagnosis, Humans, Paired Box Transcription Factors, Abnormalities, Multiple, Female, Chromosome Deletion, PAX3 Transcription Factor, Spinal Dysraphism
Abstract: Interstitial 2q36 deletion is a rare event. Only two previously published cases of 2q36 deletions were characterized using array-CGH. This is the first case diagnosed prenatally.We report on the prenatal diagnosis of a 2q36.1q36.3 interstitial deletion in a fetus with facial dysmorphism, spina bifida, and cleft palate.Array-CGH analysis revealed a 5.6 Mb interstitial deletion of the long arm of chromosome 2q36.1q36.3, including the PAX3 and EPHA4 genes.The present study reinforces the hypothesis that PAX3 haploinsufficiency may be associated with neural tube defects in humans and suggests that the EPHA4 gene might be implicated during palate development. This report also illustrates the added value of array-CGH to detect cryptic chromosomal imbalances in malformed fetuses and to improve genetic counseling prenatally.
Published: 2013

19. Prenatal detection of cryptic rearrangements by multiplex ligation probe amplification in fetuses with ultrasound abnormalities

Author: Anne Debost-Legrand, Céline Pebrel-Richard, Andrei Tchirkov, Carole Goumy, Lauren Veronese, Khadidja Haoud, Laetitia Gouas, Philippe Vago, and Eleonore Eymard-Pierre
Subjects: Adult, Pathology, medicine.medical_specialty, Genetic counseling, Molecular Probe Techniques, Prenatal diagnosis, Biology, Ultrasonography, Prenatal, Young Adult, Fetus, Pregnancy, medicine, Humans, Multiplex, Multiplex ligation-dependent probe amplification, Genetic Testing, Prospective Studies, Genetics (clinical), In Situ Hybridization, Fluorescence, Genetic testing, Chromosome Aberrations, Gene Rearrangement, medicine.diagnostic_test, Gene rearrangement, Nucleic acid amplification technique, Telomere, Karyotyping, Female, Ligation, Nucleic Acid Amplification Techniques
Abstract: Purpose: Congenital malformations are a major cause of morbidity and mortality in newborn infants, and genomic imbalances are a significant component of their etiology. The aim of this study was to evaluate the ability of prenatal multiplex ligation probe amplification screening to detect cryptic chromosomal imbalances in fetuses with ultrasound abnormalities of unknown etiology. Methods: Multiplex ligation probe amplification was performed with three separate sets of probes: two for subtelomeric regions and one for mental retardation syndrome loci. Sixty-one fetuses with significant ultrasound anomalies and normal karyotype at a minimum of 400-band resolution were tested between January 2007 and January 2009. Results: We identified four unbalanced rearrangements: one del 18pter/amp 5pter, one del 9pter, one 15q11q13 microdeletion, and one 22q11 microdeletion with atypical presentation. After genetic counseling, two of the pregnancies were terminated. Conclusion: Multiplex ligation probe amplification analysis was able to identify clinically significant rearrangements in 6.5% of fetuses with prenatally identified sonographic abnormalities. This prospective study highlights that multiplex ligation probe amplification screening of fetuses with ultrasound abnormalities in the prenatal period is technically feasible and relevant for diagnosis and prognosis. Genet Med 2010:12(6):376–380.
Published: 2010

20. Small 6q16.1 Deletions Encompassing POU3F2 Cause Susceptibility to Obesity and Variable Developmental Delay with Intellectual Disability

Author: Encarna Guillén-Navarro, Ann Nordgren, Agne Liedén, Ronnie Wright, Chiara Pantaleoni, María Juliana Ballesta-Martínez, Philippe M. Campeau, Meriel McEntagart, Katherine E. Schertz, Céline Pebrel-Richard, Silvia Annunziata, Megan Thomas, Peter E. Clayton, Cristina Hernando, Catherine Sarret, Paul R. Kasher, Bronwyn Kerr, Tiziana Granata, Jennifer L. Eaton, Caroline E. Laverriere, Francesca L. Sciacca, Eric Glasgow, Adam Jackson, Olaya Villa-Marcos, Siddharth Banka, INGEMM, Institute of Medical and Molecular Genetics, Center for Medical Genetics, Head of the Department of Medical Genetics, Molecular Medicine and Surgery department, Karolinska Institutet [Stockholm], CHU Clermont-Ferrand, Institut Pascal (IP), SIGMA Clermont (SIGMA Clermont)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Regional Genetic Service, St Mary's Hospital, Manchester, and SIGMA Clermont (SIGMA Clermont)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, obesity, Morpholino, Body Mass Index, 0302 clinical medicine, Intellectual disability, Basic Helix-Loop-Helix Transcription Factors, Genetics(clinical), Child, Zebrafish, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Sequence Deletion, Genetics, biology, Middle Aged, Phenotype, Pedigree, intellectual disability, Child, Preschool, SIM1, Chromosomes, Human, Pair 6, Female, Melanocortin, Adult, Adolescent, POU3F2 (also called BRN2 or N-OCT3 or OCT7), 6q16, Hypothalamus, Cell Line, Young Adult, 03 medical and health sciences, Report, oxytocin, medicine, Animals, Humans, Gene, Transcription factor, Homeodomain Proteins, medicine.disease, biology.organism_classification, Repressor Proteins, Disease Models, Animal, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, POU Domain Factors, Energy Metabolism, 030217 neurology & neurosurgery
Abstract: Genetic studies of intellectual disability and identification of monogenic causes of obesity in humans have made immense contribution toward the understanding of the brain and control of body mass. The leptin > melanocortin > SIM1 pathway is dysregulated in multiple monogenic human obesity syndromes but its downstream targets are still unknown. In ten individuals from six families, with overlapping 6q16.1 deletions, we describe a disorder of variable developmental delay, intellectual disability, and susceptibility to obesity and hyperphagia. The 6q16.1 deletions segregated with the phenotype in multiplex families and were shown to be de novo in four families, and there was dramatic phenotypic overlap among affected individuals who were independently ascertained without bias from clinical features. Analysis of the deletions revealed a ∼350 kb critical region on chromosome 6q16.1 that encompasses a gene for proneuronal transcription factor POU3F2, which is important for hypothalamic development and function. Using morpholino and mutant zebrafish models, we show that POU3F2 lies downstream of SIM1 and controls oxytocin expression in the hypothalamic neuroendocrine preoptic area. We show that this finding is consistent with the expression patterns of POU3F2 and related genes in the human brain. Our work helps to further delineate the neuro-endocrine control of energy balance/body mass and demonstrates that this molecular pathway is conserved across multiple species.
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20 results on '"Céline Pebrel‐Richard"'

1. Is an association of acro-osteolysis, bone fragility, and enchondromatosis a newfound disease caused by an amplification of PTHLH? A case report

2. Hemizygous FGG p.Ala108Gly in a hypofibrinogenemic patient with a heterozygous 14.8 Mb deletion encompassing the entire fibrinogen gene cluster

3. Neurodevelopmental phenotype in 36 new patients with 8p inverted duplication-deletion: Genotype-phenotype correlation for anomalies of the corpus callosum

4. Optical genome mapping enables constitutional chromosomal aberration detection

5. Analysis of the cost effectiveness of different strategies for the antenatal diagnosis of chromosomal aberrations in cases of ultrasound-identified fetal abnormalities

6. Further refining the critical region of 10q26 microdeletion syndrome: A possible involvement of INSYN2 and NPS in the cognitive phenotype

7. Whole genome paired-end sequencing elucidates functional and phenotypic consequences of balanced chromosomal rearrangement in patients with developmental disorders

8. Spatial organization of chromosome territories in the interphase nucleus of trisomy 21 cells

9. Is BRCA2 involved in early onset colorectal cancer risk?

10. A French multicenter study of over 700 patients with 22q11 deletions diagnosed using FISH or aCGH

11. Sperm meiotic segregation of a balanced interchromosomal reciprocal insertion resulting in recurrent spontaneous miscarriage

12. Congenital diaphragmatic hernia may be associated with 17q12 microdeletion syndrome

13. Clinical and molecular description of a 17q21.33 microduplication in a girl with severe kyphoscoliosis and developmental delay

14. Impaired Presynaptic High-Affinity Choline Transporter Causes a Congenital Myasthenic Syndrome with Episodic Apnea

15. A new case of 8q22.1 microdeletion restricts the critical region for Nablus mask-like facial syndrome

16. An atypical 0.8 Mb inherited duplication of 22q11.2 associated with psychomotor impairment

17. Prenatal Screening of 21 Microdeletion/Microduplication Syndromes and Subtelomeric Imbalances by MLPA in Fetuses with Increased Nuchal Translucency and Normal Karyotype

18. De novo 2q36.1q36.3 interstitial deletion involving the PAX3 and EPHA4 genes in a fetus with spina bifida and cleft palate

19. Prenatal detection of cryptic rearrangements by multiplex ligation probe amplification in fetuses with ultrasound abnormalities

20. Small 6q16.1 Deletions Encompassing POU3F2 Cause Susceptibility to Obesity and Variable Developmental Delay with Intellectual Disability

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20 results on '"Céline Pebrel‐Richard"'

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