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Targeted gene capture and massively parallel sequencing identify TMC1 as the causative gene in a six‐generation Chinese family with autosomal dominant hearing loss
Author(s) -
Gao Xue,
Huang ShaSha,
Yuan YongYi,
Wang GuoJian,
Xu JinCao,
Ji YuBin,
Han MingYu,
Yu Fei,
Kang DongYang,
Lin Xi,
Dai Pu
Publication year - 2015
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37206
Subject(s) - hearing loss , genetics , massive parallel sequencing , biology , mutation , gene , population , dna sequencing , medicine , audiology , environmental health
Hereditary nonsyndromic hearing loss is extremely heterogeneous. Mutations in the transmembrane channel‐like gene1 ( TMC1 ) are known to cause autosomal dominant and recessive forms of nonsyndromic hearing loss linked to the loci of DFNA36 and DFNB7/11, respectively. We characterized a six‐generation Chinese family (5315) with progressive, postlingual autosomal dominant nonsyndromic hearing loss (ADNSHL). By combining targeted capture of 82 known deafness genes, next‐generation sequencing and bioinformatic analysis, we identified TMC1 c.1714G>A (p. D572N) as the disease‐causing mutation. This mutation co‐segregated with hearing loss in other family members and was not detected in 308 normal controls. In order to determine the prevalence of TMC1 c.1714G>A in Chinese ADNSHL families, we used DNA samples from 67 ADNSHL families with sloping audiogram and identified two families carry this mutation. To determine whether it arose from a common ancestor, we analyzed nine STR markers. Our results indicated that TMC1 c.1714G>A (p.D572N) account for about 4.4% (3/68) of ADNSHL in the Chinese population. © 2015 Wiley Periodicals, Inc.