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

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 invol... Mehr ...

Verfasser: Seco, Celia Zazo
Wesdorp, Mieke
Feenstra, Ilse
Pfundt, Rolph
Hehir-Kwa, Jayne Y.
Lelieveld, Stefan H.
Castelein, Steven
Gilissen, Christian
de Wijs, Ilse J.
Admiraal, Ronald J. C.
Pennings, Ronald J. E.
Kunst, Henricus P. M.
van de Kamp, Jiddeke M.
Tamminga, Saskia
Houweling, Arjan C.
Plomp, Astrid S.
Maas, Saskia M.
Gans, Pia A. M. de Koning
Kant, Sarina G.
de Geus, Christa M.
Frints, Suzanna G. M.
Vanhoutte, Els K.
van Dooren, Marieke F.
van den Boogaard, Marie-Jose H.
Scheffer, Hans
Nelen, Marcel
Kremer, Hannie
Hoefsloot, Lies
Schraders, Margit
Yntema, Helger G.
Dokumenttyp: Artikel
Erscheinungsdatum: 2017
Reihe/Periodikum: Seco , C Z , Wesdorp , M , Feenstra , I , Pfundt , R , Hehir-Kwa , J Y , Lelieveld , S H , Castelein , S , Gilissen , C , de Wijs , I J , Admiraal , R J C , Pennings , R J E , Kunst , H P M , van de Kamp , J M , Tamminga , S , Houweling , A C , Plomp , A S , Maas , S M , Gans , P A M D K , Kant , S G , de Geus , C M , Frints , S G M , Vanhoutte , E K , van Dooren , M F , van den Boogaard , M-J H , Scheffer , H , Nelen , M , Kremer , H , Hoefsloot , L , Schraders , M & Yntema , H G 2017 , ' The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands ' , European Journal of Human Genetics , vol. 25 , no. 3 , pp. 308-314 . https://doi.org/10.1038/ejhg.2016.182
Schlagwörter: COPY NUMBER VARIANTS / MUTATION / DEAFNESS / IDENTIFICATION / FREQUENCY / OTOGELIN / SPECTRUM / EAR
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-28774395
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://cris.maastrichtuniversity.nl/en/publications/34d000c1-d1d8-4d5b-811f-bf400d1099d7

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.