Targeted gene capture and massively parallel sequencing identify TMC1 as the causative gene in a six-generation Chinese family with autosomal dominant hearing loss.
Targeted gene capture and massively parallel sequencing identify TMC1 as the causative gene in a six-generation Chinese family with autosomal dominant hearing loss.
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DOI：
10.1002/ajmg.a.37206
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发表时间：
2015-10
期刊：
影响因子：
--
通讯作者：
Dai P
中科院分区：
文献类型：
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作者：
Gao X;Huang SS;Yuan YY;Wang GJ;Xu JC;Ji YB;Han MY;Yu F;Kang DY;Lin X;Dai P
遗传性非综合征性听力损失是非常异质性的。已知跨膜通道样基因1（TMC 1）的突变分别导致与DFNA 36和DFNB 7/11基因座相关的常染色体显性和隐性形式的非综合征性听力损失。我们描述了一个六代共5315人的进行性常染色体显性非综合征性耳聋（ADNSHL）家系。通过结合82个已知耳聋基因的靶向捕获、下一代测序和生物信息学分析，我们确定TMC 1 c.1714G>A（p.D572N）为致病突变。该突变与其他家族成员的听力损失共分离，在308名正常对照中未检测到。为了解TMC1c.1714G>A在中国人ADNSHL家系中的流行情况，我们对67个有听力倾斜的ADNSHL家系进行了DNA检测，并鉴定出2个携带该突变的家系。为了确定它是否来自一个共同的祖先，我们分析了9个STR标记。结果表明，TMC 1c.1714G>A（p.D572N）基因在中国人群中约占ADNSHL基因的4.4%（3/68）。
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.