| Literature DB >> 28000701 |
Celia Zazo Seco1,2, Mieke Wesdorp1,2, Ilse Feenstra3, Rolph Pfundt2,3, Jayne Y Hehir-Kwa2,3, Stefan H Lelieveld3, Steven Castelein3, Christian Gilissen3, Ilse J de Wijs3, Ronald Jc Admiraal1,2, Ronald Je Pennings1,4, Henricus Pm Kunst1,4, Jiddeke M van de Kamp5, Saskia Tamminga5, Arjan C Houweling5, Astrid S Plomp6, Saskia M Maas6,7, Pia Am de Koning Gans8, Sarina G Kant8, Christa M de Geus9, Suzanna Gm Frints10, Els K Vanhoutte10, Marieke F van Dooren11, Marie-José H van den Boogaard12, Hans Scheffer2,3, Marcel Nelen3, Hannie Kremer1,2,3, Lies Hoefsloot3,11, Margit Schraders1,2, Helger G Yntema2,3.
Abstract
Hearing impairment (HI) is genetically heterogeneous which hampers genetic counseling and molecular diagnosis. Testing of several single HI-related genes is laborious and expensive. In this study, we evaluate the diagnostic utility of whole-exome sequencing (WES) targeting a panel of HI-related genes. Two hundred index patients, mostly of Dutch origin, with presumed hereditary HI underwent WES followed by targeted analysis of an HI gene panel of 120 genes. We found causative variants underlying the HI in 67 of 200 patients (33.5%). Eight of these patients have a large homozygous deletion involving STRC, OTOA or USH2A, which could only be identified by copy number variation detection. Variants of uncertain significance were found in 10 patients (5.0%). In the remaining 123 cases, no potentially causative variants were detected (61.5%). In our patient cohort, causative variants in GJB2, USH2A, MYO15A and STRC, and in MYO6 were the leading causes for autosomal recessive and dominant HI, respectively. Segregation analysis and functional analyses of variants of uncertain significance will probably further increase the diagnostic yield of WES.Entities:
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Year: 2016 PMID： 28000701 PMCID： PMC5315517 DOI： 10.1038/ejhg.2016.182
Source DB: PubMed Journal: Eur J Hum Genet ISSN： 1018-4813 Impact factor: 4.246