Combined genetic approaches yield a 48% diagnostic rate in a large cohort of French hearing-impaired patients. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Baux, D.; Vaché, C.; Blanchet, C.; Willems, M.; Baudoin, C.; Moclyn, M.; Faugère, V.; Touraine, R.; Isidor, B.; Dupin-Deguine, D.; Nizon, M.; Vincent, M.; Mercier, S.; Calais, C.; García-García, G.; Azher, Z.; Lambert, L.; Perdomo-Trujillo, Y.; Giuliano, F.; Claustres, M.; Koenig, M.; Mondain, M.; Roux, A.
• Is Part Of: Scientific reports. Volume 7:Issue 1(2017)
• Page Start: 1
• Page End: 10
• Publication Date: 2017-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-017-16846-9
• Languages: English
• ISSNs: 2045-2322

Abstract

Abstract 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 forSTRC . This comprehensive screening yielded an overall diagnostic rate of 48%, equally distributed betweenDFNB1 (24%) and the other genes (24%). Pathogenic genotypes were identified in 19 different genes, with a high prevalence ofGJB2, STRC, MYO15A, OTOF, TMC1, MYO7A andUSH2A . Involvement of an Usher gene was reported in 16% of the genotyped cohort. Fourde 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.