21 results on '"Pacault M"'
Search Results
2. E-255 Catheter blood vessel ratio for middle cerebral artery occlusions requiring mechanical thrombectomy: a propensity adjusted analysis
- Author
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Catapano, J, primary, Naik, A, additional, Pacault, M, additional, Sigh, R, additional, Stonnington, H, additional, Rangel, I, additional, Koester, S, additional, Winkler, E, additional, Desai, S, additional, Jadhav, A, additional, Albuquerque, F, additional, and Ducruet, A, additional
- Published
- 2022
- Full Text
- View/download PDF
3. Les soignants face aux patients non vaccinés.
- Author
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Pacault, M., primary
- Published
- 2022
- Full Text
- View/download PDF
4. Platelet function analyser (PFA-100) results and von Willebrand factor deficiency: a 16-year ‘real-world’ experience
- Author
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ARDILLON, L., TERNISIEN, C., FOUASSIER, M., SIGAUD, M., LEFRANÇOIS, A., PACAULT, M., RIBEYROL, O., FRESSINAUD, E., BOISSEAU, P., and TROSSAËRT, M.
- Published
- 2015
- Full Text
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5. E-123 Middle meningeal artery embolization for chronic subdural hematomas: an institutional analysis
- Author
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Catapano, J, primary, Nguyen, C, additional, Pacault, M, additional, Cole, T, additional, Baranoski, J, additional, Wilkinson, D, additional, Majmundar, N, additional, Ducruet, A, additional, and Albuquerque, F, additional
- Published
- 2020
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- View/download PDF
6. Identification of a new VHL exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease
- Author
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Lenglet, M. Robriquet, F. Schwarz, K. Camps, C. Couturier, A. Hoogewijs, D. Buffet, A. Knight, S.J.L. Gad, S. Couvé, S. Chesnel, F. Pacault, M. Lindenbaum, P. Job, S. Dumont, S. Besnard, T. Cornec, M. Dreau, H. Pentony, M. Kvikstad, E. Deveaux, S. Burnichon, N. Ferlicot, S. Vilaine, M. Mazzella, J.-M. Airaud, F. Garrec, C. Heidet, L. Irtan, S. Mantadakis, E. Bouchireb, K. Debatin, K.-M. Redon, R. Bezieau, S. Brigitte Bressac-de, P. Teh, B.T. Girodon, F. Randi, M.-L. Putti, M.C. Bours, V. Van Wijk, R. Göthert, J.R. Kattamis, A. Janin, N. Bento, C. Taylor, J.C. Arlot-Bonnemains, Y. Richard, S. Gimenez-Roqueplo, A.-P. Cario, H. Gardie, B.
- Subjects
endocrine system diseases ,urologic and male genital diseases ,neoplasms ,female genital diseases and pregnancy complications - Abstract
Chuvash polycythemia is an autosomal recessive form of erythrocytosis associated with a homozygous p.Arg200Trp mutation in the von Hippel-Lindau (VHL) gene. Since this discovery, additional VHL mutations have been identified in patients with congenital erythrocytosis, in a homozygous or compound-heterozygous state. VHL is a major tumor suppressor gene, mutations in which were first described in patients presenting with VHL disease, which is characterized by the development of highly vascularized tumors. Here, we identify a new VHL cryptic exon (termed E19) deep in intron 1 that is naturally expressed in many tissues. More importantly, we identify mutations in E19 in 7 families with erythrocytosis (1 homozygous case and 6 compound-heterozygous cases with a mutation in E19 in addition to a mutation in VHL coding sequences) and in 1 large family with typical VHL disease but without any alteration in the other VHL exons. In this study, we show that the mutations induced a dysregulation of VHL splicing with excessive retention of E19 and were associated with a downregulation of VHL protein expression. In addition, we demonstrate a pathogenic role for synonymous mutations in VHL exon 2 that altered splicing through E2-skipping in 5 families with erythrocytosis or VHL disease. In all the studied cases, the mutations differentially affected splicing, correlating with phenotype severity. This study demonstrates that cryptic exon retention and exon skipping are new VHL alterations and reveals a novel complex splicing regulation of the VHL gene. These findings open new avenues for diagnosis and research regarding the VHL-related hypoxia-signaling pathway. © 2018 by The American Society of Hematology.
- Published
- 2018
7. Équipe mobile de vaccination Grippe intra CHU
- Author
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Pacault, M., primary, Prizzi, M., additional, Veteau, M., additional, and Garcia Munne, E., additional
- Published
- 2019
- Full Text
- View/download PDF
8. La consultation du voyage par les infirmières déléguées
- Author
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Pacault, M., primary, Veteau, M., additional, and Prizzi, M., additional
- Published
- 2018
- Full Text
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9. L’expression de la 11 béta-hydroxystéroïde déshydrogénase de type 1 (11-BHSD1) est augmentée dans le tissu adipeux sous-cutané des obèses diabétiques
- Author
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Le Loupp, A.G., primary, Pacault, M., additional, Letessier, E., additional, Kubis, C., additional, Prieur, X., additional, Drui, D., additional, Bach, K., additional, and Cariou, B., additional
- Published
- 2015
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10. Uncommon MET mutational landscape in a non-small cell lung cancer patient treated with crizotinib: Case report.
- Author
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Geier M, Nguyen J, Dhamelincourt E, Babey H, Descourt R, Quéré G, Robinet G, Lucia F, and Pacault M
- Abstract
Background: MET exon 14 ( MET ex14) skipping mutations are oncogenic drivers observed in approximately 3-4% of non-small cell lung cancers (NSCLC). Several distinct genetic alterations leading to METex14 have been reported but clinical significances of rare mutations are not well defined as well as outcomes of patients upon MET inhibitors (METi)., Case Presentation: This report presents the case of a patient with metastatic NSCLC harboring an uncommon MET mutational landscape including notably a novel MET ex14 mutation (R1022L). Dramatic but transient efficacy was observed under crizotinib, due to early occurrence of acquired both on- and off-target mechanisms of resistance such as MET D1246H mutation and wild-type KRAS amplification., Conclusion: Our case provides additional data on MET rare oncogenic variants and their sensitivity to METi. Systematic assessment of post-tyrosine kinase inhibitor tumor sample remains critical to identify on- and off-target mechanisms that may represent therapeutically targetable drivers in resistant patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
- Published
- 2024
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11. Characterization of genetic variants in the EGLN1/PHD2 gene identified in a European collection of patients with erythrocytosis.
- Author
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Delamare M, Le Roy A, Pacault M, Schmitt L, Garrec C, Maaziz N, Myllykoski M, Rimbert A, Karaghiannis V, Aral B, Catherwood M, Airaud F, Mansour-Hendili L, Hoogewijs D, Peroni E, Idriss S, Lesieur V, Caillaud A, Si-Tayeb K, Chariau C, Gaignerie A, Rab M, Haferlach T, Meggendorfer M, Bézieau S, Benetti A, Casadevall N, Hirsch P, Rose C, Wemeau M, Galacteros F, Cassinat B, Bellosillo B, Bento C, Van Wijk R, Petrides PE, Randi ML, McMullin MF, Koivunen P, Girodon F, and Gardie B
- Subjects
- Humans, Hypoxia-Inducible Factor-Proline Dioxygenases genetics, Hypoxia-Inducible Factor-Proline Dioxygenases metabolism, Germ-Line Mutation, Base Sequence, Polycythemia diagnosis, Polycythemia genetics, Polycythemia metabolism
- Abstract
Hereditary erythrocytosis is a rare hematologic disorder characterized by an excess of red blood cell production. Here we describe a European collaborative study involving a collection of 2,160 patients with erythrocytosis sequenced in ten different laboratories. We focused our study on the EGLN1 gene and identified 39 germline missense variants including one gene deletion in 47 probands. EGLN1 encodes the PHD2 prolyl 4-hydroxylase, a major inhibitor of hypoxia-inducible factor. We performed a comprehensive study to evaluate the causal role of the identified PHD2 variants: (i) in silico studies of localization, conservation, and deleterious effects; (ii) analysis of hematologic parameters of carriers identified in the UK Biobank; (iii) functional studies of the protein activity and stability; and (iv) a comprehensive study of PHD2 splicing. Altogether, these studies allowed the classification of 16 pathogenic or likely pathogenic mutants in a total of 48 patients and relatives. The in silico studies extended to the variants described in the literature showed that a minority of PHD2 variants can be classified as pathogenic (36/96), without any differences from the variants of unknown significance regarding the severity of the developed disease (hematologic parameters and complications). Here, we demonstrated the great value of federating laboratories working on such rare disorders in order to implement the criteria required for genetic classification, a strategy that should be extended to all hereditary hematologic diseases.
- Published
- 2023
- Full Text
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12. [Towards a generalization of non-invasive prenatal diagnosis of single-gene disorders? Assesment and outlook].
- Author
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Verebi C, Gravrand V, Pacault M, Audrezet MP, Couque N, Vincent MC, Leturcq F, Tsatsaris V, Bienvenu T, and Nectoux J
- Subjects
- Pregnancy, Humans, Female, Prenatal Care, DNA genetics, France, Prenatal Diagnosis methods, Fetus
- Abstract
Objectives: The screening of fetal aneuploidies and non-invasive prenatal diagnosis of monogenic diseases (NIPD-MD) both rely on the study of free fetal DNA in maternal circulation, but their respective rise was unequal. Development of NIPD-MD has taken longer as it represents a less attractive commercial dynamic for industry, but also because it usually involves the development of tailored tests specific to each pathogenic variant., Methods: We have carried out a review of the literature on the various indications and technologies involved in the use of NIPD-MM. We present its current implementation and its development in France., Results: To date, NIPD-MD has been routinely offered in France for several years by the laboratories of the French NIPD-MD network but remains mostly limited to the exclusion of paternal or de novo variants, the exclusion DPNI-MD. Indeed, it is still difficult to study the transmission of maternal variants from circulating free DNA analysis, due to its biological complexity: coexistence and predominance of similar DNA sequences of maternal origin. Different strategies, either direct or indirect, are being evaluated to establish fetal status regardless of the parental origin of the disease or its transmission mode. The emergence of commercial screening solutions for monogenic diseases complements the arsenal of prenatal exploration tools for these diseases., Conclusion: The multitude of existing technologies and protocols may complicate the information provided during antenatal consultations, but mastery of know-how and knowledge of ethical issues of NIPD-MD will ensure optimal service and better management of pregnancies at risk of transmitting monogenic disease., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
13. Non-invasive prenatal diagnosis of single gene disorders with enhanced relative haplotype dosage analysis for diagnostic implementation.
- Author
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Pacault M, Verebi C, Champion M, Orhant L, Perrier A, Girodon E, Leturcq F, Vidaud D, Férec C, Bienvenu T, Daveau R, and Nectoux J
- Subjects
- Pregnancy, Female, Humans, Haplotypes, Prenatal Diagnosis methods, Genotype, Noninvasive Prenatal Testing methods, Cell-Free Nucleic Acids
- Abstract
Non-invasive prenatal diagnosis of single-gene disorders (SGD-NIPD) has been widely accepted, but is mostly limited to the exclusion of either paternal or de novo mutations. Indeed, it is still difficult to infer the inheritance of the maternal allele from cell-free DNA (cfDNA) analysis. Based on the study of maternal haplotype imbalance in cfDNA, relative haplotype dosage (RHDO) was developed to address this challenge. Although RHDO has been shown to be reliable, robust control of statistical error and explicit delineation of critical parameters for assessing the quality of the analysis have not been fully addressed. We present here a universal and adaptable enhanced-RHDO (eRHDO) procedure through an automated bioinformatics pipeline with a didactic visualization of the results, aiming to be applied for any SGD-NIPD in routine care. A training cohort of 43 families carrying CFTR, NF1, DMD, or F8 mutations allowed the characterization and optimal setting of several adjustable data variables, such as minimum sequencing depth, type 1 and type 2 statistical errors, as well as the quality assessment of intermediate steps and final results by block score and concordance score. Validation was successfully performed on a test cohort of 56 pregnancies. Finally, computer simulations were used to estimate the effect of fetal-fraction, sequencing depth and number of informative SNPs on the quality of results. Our workflow proved to be robust, as we obtained conclusive and correctly inferred fetal genotypes in 94.9% of cases, with no false-negative or false-positive results. By standardizing data generation and analysis, we fully describe a turnkey protocol for laboratories wishing to offer eRHDO-based non-invasive prenatal diagnosis for single-gene disorders as an alternative to conventional prenatal diagnosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pacault et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2023
- Full Text
- View/download PDF
14. Non-invasive prenatal diagnosis of single gene disorders by paternal mutation exclusion: 3 years of clinical experience.
- Author
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Pacault M, Verebi C, Lopez M, Vaucouleur N, Orhant L, Deburgrave N, Leturcq F, Vidaud D, Girodon E, Bienvenu T, and Nectoux J
- Subjects
- Aneuploidy, Child, Female, Humans, Male, Mutation, Paternal Inheritance, Polymerase Chain Reaction methods, Pregnancy, Prenatal Diagnosis methods, Cell-Free Nucleic Acids, Noninvasive Prenatal Testing
- Abstract
Objectives: Cell-free fetal DNA (cffDNA) analysis is performed routinely for aneuploidy screening, RhD genotyping or sex determination. Although applications to single gene disorders (SGD) are being rapidly developed worldwide, only a few laboratories offer cffDNA testing routinely as a diagnosis service for this indication. In a previous report, we described a standardised protocol for non-invasive exclusion of paternal variant in SGD. Three years later, we now report our clinical experience with the protocol., Design: Descriptive study., Setting: Multi-centre French., Population: Indications for referral included pregnancies at risk of 25% or 50% of paternally inherited SGD, and pregnancies associated with an increased risk of SGD due to a de novo variant, either from strongly suggestive ultrasound findings or from a possible parental germinal mosaicism in the context of a previously affected child., Methods: Non-invasive prenatal diagnosis was performed using custom assays for droplet digital PCR. Feasibility, diagnostic performance and turn-around time were evaluated., Results: Mean time for a new assay design and validation was evaluated at 14 days, and mean result reporting time was 6 days. All referred pathogenic variants could be targeted except one located in a complex genomic region. A result was obtained for every 198 referrals except two., Conclusion: This service was successfully implemented as a routine laboratory practice. It has been widely adopted by French clinicians and patients for paternal variant exclusion in various disorders., Tweetable Abstract: A robust approach to non-invasive prenatal exclusion of paternal pathogenic variant in a diagnosis setting., (© 2022 John Wiley & Sons Ltd.)
- Published
- 2022
- Full Text
- View/download PDF
15. A de novo 2q37.2 deletion encompassing AGAP1 and SH3BP4 in a patient with autism and intellectual disability.
- Author
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Pacault M, Nizon M, Pichon O, Vincent M, Le Caignec C, and Isidor B
- Subjects
- Adaptor Proteins, Signal Transducing genetics, Autistic Disorder pathology, Child, Chromosome Deletion, Chromosomes, Human, Pair 2 genetics, GTPase-Activating Proteins genetics, Humans, Intellectual Disability pathology, Male, Autistic Disorder genetics, Intellectual Disability genetics
- Abstract
Autism spectrum disorders are complex neurodevelopmental syndromes characterized by phenotypic and genetic heterogeneity. Further identification of causal genes may help in better understanding the underlying mechanisms of the disorder, thus improving the patients' management. To date, abnormal synaptogenesis is thought to be one of the major underlying causes of autism spectrum disorders. Here, using oligoarray-based comparative genomic hybridization, we identified a de novo deletion at 2q37.2 locus spanning 1 Mb and encompassing AGAP1 and SH3BP4, in a boy with autism and intellectual disability. Both genes have been described as being involved in endosomal trafficking, and AGAP1 in particular has been shown to be expressed in the developing brain and to play a role in dendritic spine formation and synapse function, making it a potential causative gene to our patient's phenotype., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
16. New splicing pathogenic variant in EBP causing extreme familial variability of Conradi-Hünermann-Happle Syndrome.
- Author
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Pacault M, Vincent M, Besnard T, Kannengiesser C, Bénéteau C, Barbarot S, Latypova X, Belabbas K, Lamazière A, Winer N, Joubert M, Bézieau S, Isidor B, Mercier S, Nizon M, Leclerc-Mercier S, Hadj-Rabia S, and Dufernez F
- Subjects
- Aborted Fetus abnormalities, Adult, Chondrodysplasia Punctata pathology, Female, Humans, Male, Pedigree, RNA Splicing, Chondrodysplasia Punctata genetics, Mutation, Phenotype, Steroid Isomerases genetics
- Abstract
X-linked dominant chondrodysplasia punctata (CDPX2 or Conradi-Hünermann-Happle syndrome, MIM #302960) is caused by mutations in the EBP gene. Affected female patients present with Blaschkolinear ichthyosis, coarse hair or alopecia, short stature, and normal psychomotor development. The disease is usually lethal in boys. Nevertheless, few male patients have been reported; they carry a somatic mosaicism in EBP or present with Klinefelter syndrome. Here, we report CDPX2 patients belonging to a three-generation family, carrying the splice variant c.301 + 5 G > C in intron 2 of EBP. The grandfather carries the variant as mosaic state and presents with short stature and mild ichthyosis. The mother also presents with short stature and mild ichthyosis and the female fetus with severe limb and vertebrae abnormalities and no skin lesions, with random X inactivation in both. This further characterizes the phenotypical spectrum of CDPX2, as well as intrafamilial variability, and raises the question of differential EBP mRNA splicing between the different target tissues.
- Published
- 2018
- Full Text
- View/download PDF
17. NBEA: Developmental disease gene with early generalized epilepsy phenotypes.
- Author
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Mulhern MS, Stumpel C, Stong N, Brunner HG, Bier L, Lippa N, Riviello J, Rouhl RPW, Kempers M, Pfundt R, Stegmann APA, Kukolich MK, Telegrafi A, Lehman A, Lopez-Rangel E, Houcinat N, Barth M, den Hollander N, Hoffer MJV, Weckhuysen S, Roovers J, Djemie T, Barca D, Ceulemans B, Craiu D, Lemke JR, Korff C, Mefford HC, Meyers CT, Siegler Z, Hiatt SM, Cooper GM, Bebin EM, Snijders Blok L, Veenstra-Knol HE, Baugh EH, Brilstra EH, Volker-Touw CML, van Binsbergen E, Revah-Politi A, Pereira E, McBrian D, Pacault M, Isidor B, Le Caignec C, Gilbert-Dussardier B, Bilan F, Heinzen EL, Goldstein DB, Stevens SJC, and Sands TT
- Subjects
- Adolescent, Child, Child, Preschool, Epilepsy, Generalized genetics, Female, Genotype, Humans, Male, Mutation, Phenotype, Carrier Proteins genetics, Nerve Tissue Proteins genetics, Neurodevelopmental Disorders genetics
- Abstract
NBEA is a candidate gene for autism, and de novo variants have been reported in neurodevelopmental disease (NDD) cohorts. However, NBEA has not been rigorously evaluated as a disease gene, and associated phenotypes have not been delineated. We identified 24 de novo NBEA variants in patients with NDD, establishing NBEA as an NDD gene. Most patients had epilepsy with onset in the first few years of life, often characterized by generalized seizure types, including myoclonic and atonic seizures. Our data show a broader phenotypic spectrum than previously described, including a myoclonic-astatic epilepsy-like phenotype in a subset of patients. Ann Neurol 2018;84:796-803., (© 2018 American Neurological Association.)
- Published
- 2018
- Full Text
- View/download PDF
18. Identification of a new VHL exon and complex splicing alterations in familial erythrocytosis or von Hippel-Lindau disease.
- Author
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Lenglet M, Robriquet F, Schwarz K, Camps C, Couturier A, Hoogewijs D, Buffet A, Knight SJL, Gad S, Couvé S, Chesnel F, Pacault M, Lindenbaum P, Job S, Dumont S, Besnard T, Cornec M, Dreau H, Pentony M, Kvikstad E, Deveaux S, Burnichon N, Ferlicot S, Vilaine M, Mazzella JM, Airaud F, Garrec C, Heidet L, Irtan S, Mantadakis E, Bouchireb K, Debatin KM, Redon R, Bezieau S, Bressac-de Paillerets B, Teh BT, Girodon F, Randi ML, Putti MC, Bours V, Van Wijk R, Göthert JR, Kattamis A, Janin N, Bento C, Taylor JC, Arlot-Bonnemains Y, Richard S, Gimenez-Roqueplo AP, Cario H, and Gardie B
- Subjects
- Adolescent, Adult, Child, Female, Heterozygote, Humans, Male, Middle Aged, Pedigree, Polycythemia classification, Polycythemia pathology, Young Adult, von Hippel-Lindau Disease pathology, Exons, Genetic Predisposition to Disease, Mutation, Polycythemia genetics, RNA Splicing, Von Hippel-Lindau Tumor Suppressor Protein genetics, von Hippel-Lindau Disease genetics
- Abstract
Chuvash polycythemia is an autosomal recessive form of erythrocytosis associated with a homozygous p.Arg200Trp mutation in the von Hippel-Lindau ( VHL ) gene. Since this discovery, additional VHL mutations have been identified in patients with congenital erythrocytosis, in a homozygous or compound-heterozygous state. VHL is a major tumor suppressor gene, mutations in which were first described in patients presenting with VHL disease, which is characterized by the development of highly vascularized tumors. Here, we identify a new VHL cryptic exon (termed E1') deep in intron 1 that is naturally expressed in many tissues. More importantly, we identify mutations in E1' in 7 families with erythrocytosis (1 homozygous case and 6 compound-heterozygous cases with a mutation in E1' in addition to a mutation in VHL coding sequences) and in 1 large family with typical VHL disease but without any alteration in the other VHL exons. In this study, we show that the mutations induced a dysregulation of VHL splicing with excessive retention of E1' and were associated with a downregulation of VHL protein expression. In addition, we demonstrate a pathogenic role for synonymous mutations in VHL exon 2 that altered splicing through E2-skipping in 5 families with erythrocytosis or VHL disease. In all the studied cases, the mutations differentially affected splicing, correlating with phenotype severity. This study demonstrates that cryptic exon retention and exon skipping are new VHL alterations and reveals a novel complex splicing regulation of the VHL gene. These findings open new avenues for diagnosis and research regarding the VHL-related hypoxia-signaling pathway., (© 2018 by The American Society of Hematology.)
- Published
- 2018
- Full Text
- View/download PDF
19. Non-invasive prenatal diagnosis of paternally inherited disorders from maternal plasma: detection of NF1 and CFTR mutations using droplet digital PCR.
- Author
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Gruber A, Pacault M, El Khattabi LA, Vaucouleur N, Orhant L, Bienvenu T, Girodon E, Vidaud D, Leturcq F, Costa C, Letourneur F, Anselem O, Tsatsaris V, Goffinet F, Viot G, Vidaud M, and Nectoux J
- Subjects
- Female, Genotype, Humans, Male, Neurodevelopmental Disorders blood, Neurodevelopmental Disorders genetics, Neurofibromatosis 1 blood, Neurofibromatosis 1 diagnosis, Cystic Fibrosis Transmembrane Conductance Regulator genetics, Mutation, Neurodevelopmental Disorders diagnosis, Neurofibromatosis 1 genetics, Polymerase Chain Reaction, Prenatal Diagnosis
- Abstract
Background: To limit risks of miscarriages associated with invasive procedures of current prenatal diagnosis practice, we aim to develop a personalized medicine-based protocol for non-invasive prenatal diagnosis (NIPD) of monogenic disorders relying on the detection of paternally inherited mutations in maternal blood using droplet digital PCR (ddPCR)., Methods: This study included four couples at risk of transmitting paternal neurofibromatosis type 1 (NF1) mutations and four couples at risk of transmitting compound heterozygous CFTR mutations. NIPD was performed between 8 and 15 weeks of gestation, in parallel to conventional invasive diagnosis. We designed specific hydrolysis probes to detect the paternal mutation and to assess the presence of cell-free fetal DNA by ddPCR. Analytical performances of each assay were determined from paternal sample, an then fetal genotype was inferred from maternal plasma sample., Results: Presence or absence of the paternal mutant allele was correctly determined in all the studied plasma DNA samples., Conclusions: We report an NIPD protocol suitable for implementation in an experienced laboratory of molecular genetics. Our proof-of-principle results point out a high accuracy for early detection of paternal NF1 and CFTR mutations in cell-free DNA, and open new perspectives for extending the technology to NIPD of many other monogenic diseases.
- Published
- 2018
- Full Text
- View/download PDF
20. De Novo Disruption of the Proteasome Regulatory Subunit PSMD12 Causes a Syndromic Neurodevelopmental Disorder.
- Author
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Küry S, Besnard T, Ebstein F, Khan TN, Gambin T, Douglas J, Bacino CA, Craigen WJ, Sanders SJ, Lehmann A, Latypova X, Khan K, Pacault M, Sacharow S, Glaser K, Bieth E, Perrin-Sabourin L, Jacquemont ML, Cho MT, Roeder E, Denommé-Pichon AS, Monaghan KG, Yuan B, Xia F, Simon S, Bonneau D, Parent P, Gilbert-Dussardier B, Odent S, Toutain A, Pasquier L, Barbouth D, Shaw CA, Patel A, Smith JL, Bi W, Schmitt S, Deb W, Nizon M, Mercier S, Vincent M, Rooryck C, Malan V, Briceño I, Gómez A, Nugent KM, Gibson JB, Cogné B, Lupski JR, Stessman HA, Eichler EE, Retterer K, Yang Y, Redon R, Katsanis N, Rosenfeld JA, Kloetzel PM, Golzio C, Bézieau S, Stankiewicz P, and Isidor B
- Published
- 2017
- Full Text
- View/download PDF
21. Cysteinyl leukotriene signaling through perinuclear CysLT(1) receptors on vascular smooth muscle cells transduces nuclear calcium signaling and alterations of gene expression.
- Author
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Eaton A, Nagy E, Pacault M, Fauconnier J, and Bäck M
- Subjects
- Atherosclerosis metabolism, Atherosclerosis pathology, Cells, Cultured, Coronary Vessels immunology, Coronary Vessels pathology, Gene Expression Regulation, Humans, Inflammation Mediators physiology, Leukotriene C4 physiology, Lipopolysaccharides pharmacology, Muscle, Smooth, Vascular immunology, Myocytes, Smooth Muscle immunology, Plasminogen Activator Inhibitor 2 genetics, Plasminogen Activator Inhibitor 2 metabolism, Receptors, Leukotriene genetics, Transcriptional Activation, Calcium Signaling, Cell Nucleus metabolism, Muscle, Smooth, Vascular pathology, Myocytes, Smooth Muscle metabolism, Receptors, Leukotriene metabolism
- Abstract
Leukotrienes are pro-inflammatory mediators that are locally produced in coronary atherosclerotic plaques. The response induced by cysteinyl leukotrienes (CysLT) in human coronary arteries may be altered under pathological conditions, such as atherosclerosis. The aim of the present study was to elucidate cysteinyl leukotriene signaling in vascular smooth muscle cells (SMCs) and the effects of inflammation on this process. Immunohistochemical analysis of human carotid endarterectomy samples revealed that the CysLT(1) leukotriene receptor was expressed in areas that also stained positive for α-smooth muscle actin. In human coronary artery smooth muscle cells, lipopolysaccharide significantly upregulated the CysLT(1) receptor and significantly enhanced the changes in intracellular calcium induced by leukotriene C(4) (LTC(4)). In these cells, the CysLT(1) receptor exhibited a perinuclear expression, and LTC(4) stimulation predominantly enhanced nuclear calcium increase, which was significantly inhibited by the CysLT(1) receptor antagonist MK-571. Microarray analysis revealed, among a number of significantly upregulated genes after 24 h stimulation of human coronary artery smooth muscle cells with LTC(4), a 5-fold increase in mRNA levels for plasminogen activator inhibitor (PAI)-2. The LTC(4)-induced increase in PAI-2 expression was confirmed by real-time quantitative PCR and ELISA and was inhibited by the CysLT(1) receptor antagonist MK-571 and by calcium chelators. In summary, pro-inflammatory stimulation of vascular SMCs upregulated a perinuclear CysLT(1) receptor expression coupled to nuclear calcium signaling and changes in gene expression, such as upregulation of PAI-2. Taken together, these findings suggest a role of nuclear CysLT(1) receptor signaling in vascular SMCs inducing gene expression patterns associated with atherosclerosis.
- Published
- 2012
- Full Text
- View/download PDF
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