Combined genetic approaches yield a 48% diagnostic rate in a large cohort of French hearing-impaired patients
| Autor: | Z. Azher, Gema García-García, L. Lambert, B. Isidor, Christel Vaché, M. Moclyn, M. Mondain, M. Nizon, Marie-Claire Vincent, David Baux, R. Touraine, C. Calais, Y. Perdomo-Trujillo, Anne-Françoise Roux, Corinne Baudoin, F. Giuliano, Mireille Claustres, D. Dupin-Deguine, Sandra Mercier, Marjolaine Willems, Michel Koenig, Valérie Faugère, Christophe Blanchet |
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| Přispěvatelé: | Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'ORL, Hôpital Gui de Chauliac (CHRU de Montpellier), Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, CHU Saint-Etienne, Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Toulouse [Toulouse], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Strasbourg, Dpt génétique médicale [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male DNA Copy Number Variations Hearing loss Genetic counseling lcsh:Medicine Bioinformatics Sensitivity and Specificity Connexins White People Article Cohort Studies 03 medical and health sciences medicine OTOF otorhinolaryngologic diseases Humans Computer Simulation Genetic Predisposition to Disease Copy-number variation Genetic Testing Hearing Loss lcsh:Science Genetic testing Multidisciplinary Massive parallel sequencing [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE] medicine.diagnostic_test business.industry Genetic heterogeneity lcsh:R High-Throughput Nucleotide Sequencing Sequence Analysis DNA 3. Good health Connexin 26 030104 developmental biology Early Diagnosis Mutation lcsh:Q France medicine.symptom business STRC |
| Zdroj: | Scientific Reports Scientific Reports, Nature Publishing Group, 2017, 7, pp.16783. ⟨10.1038/s41598-017-16846-9⟩ Scientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) |
| ISSN: | 2045-2322 |
| Popis: | Hearing loss is the most common sensory disorder and because of its high genetic heterogeneity, implementation of Massively Parallel Sequencing (MPS) in diagnostic laboratories is greatly improving the possibilities of offering optimal care to patients. We present the results of a two-year period of molecular diagnosis that included 207 French families referred for non-syndromic hearing loss. Our multi-step strategy involved (i) DFNB1 locus analysis, (ii) MPS of 74 genes, and (iii) additional approaches including Copy Number Variations, in silico analyses, minigene studies coupled when appropriate with complete gene sequencing, and a specific assay for STRC. This comprehensive screening yielded an overall diagnostic rate of 48%, equally distributed between DFNB1 (24%) and the other genes (24%). Pathogenic genotypes were identified in 19 different genes, with a high prevalence of GJB2, STRC, MYO15A, OTOF, TMC1, MYO7A and USH2A. Involvement of an Usher gene was reported in 16% of the genotyped cohort. Four de novo variants were identified. This study highlights the need to develop several molecular approaches for efficient molecular diagnosis of hearing loss, as this is crucial for genetic counselling, audiological rehabilitation and the detection of syndromic forms. |
| Databáze: | OpenAIRE |
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