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The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands.


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.

SUBMITTER: Zazo Seco C 

PROVIDER: S-EPMC5315517 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands.

Zazo Seco Celia C   Wesdorp Mieke M   Feenstra Ilse I   Pfundt Rolph R   Hehir-Kwa Jayne Y JY   Lelieveld Stefan H SH   Castelein Steven S   Gilissen Christian C   de Wijs Ilse J IJ   Admiraal Ronald Jc RJ   Pennings Ronald Je RJ   Kunst Henricus Pm HP   van de Kamp Jiddeke M JM   Tamminga Saskia S   Houweling Arjan C AC   Plomp Astrid S AS   Maas Saskia M SM   de Koning Gans Pia Am PA   Kant Sarina G SG   de Geus Christa M CM   Frints Suzanna Gm SG   Vanhoutte Els K EK   van Dooren Marieke F MF   van den Boogaard Marie-José H MH   Scheffer Hans H   Nelen Marcel M   Kremer Hannie H   Hoefsloot Lies L   Schraders Margit M   Yntema Helger G HG  

European journal of human genetics : EJHG 20161221 3


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  ...[more]

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