Targeted Next-Generation Sequencing Successfully Detects Causative Genes in Chinese Patients with Hereditary Hearing Loss
Targeted Next-Generation Sequencing Successfully Detects Causative Genes in Chinese Patients with Hereditary Hearing Loss
复制标题
靶向下一代测序成功检测中国遗传性听力损失患者的致病基因。
DOI：
10.1089/gtmb.2016.0051
复制
发表时间：
2016-11-01
影响因子：
1.4
通讯作者：
Liu, Yuhe
中科院分区：
文献类型：
--
作者：
Chen, Siqi;Dong, Cheng;Liu, Yuhe
目的：我们尝试使用下一代测序技术（NGS）确定中国汉族人群中遗传性听力损失的遗传流行病学。材料与方法：对116名听力损失患者的GJB2、SLC26A4和GJB3基因的全长以及57个其他候选基因的外显子进行了测序。结果：在67例病例中，这60个基因中的30个潜在致病突变被确定为听力损失的可能病因。在我们的研究中，SLC26A4和GJB2是中国汉族听力损失人群中最常见的受影响基因。总的来说，它们占病例的52.8%，其次是MTRNR 1，PCDH 15和TECTA。这些数据也说明NGS可用于鉴定与遗传性听力损失有关的罕见等位基因：在30个鉴定出突变的基因中，有22个（73.3%）在遗传性听力损失中很少突变，仅占总突变频率的21.5%（42/195），每个基因的解释不超过2%。这些很少突变的基因会被常规的诊断测序方法遗漏。结论：NGS可有效地用于遗传性耳聋常见基因和罕见基因的鉴定。
Aims: We attempted to identify the genetic epidemiology of hereditary hearing loss among the Chinese Han population using next-generation sequencing (NGS). Materials and Methods: The entire length of the genes GJB2, SLC26A4, and GJB3, as well as exons of 57 additional candidate genes were sequenced from 116 individuals suffering from hearing loss. Results: Thirty potentially causative mutations from these 60 genes were identified as the likely etiologies of hearing loss in 67 of the cases. In our study, SLC26A4 and GJB2 were the most frequently affected genes among the Chinese Han population with hearing loss. Collectively, they account for 52.8% of the cases, followed by MTRNR1, PCDH15, and TECTA. These data also illustrate that NGS can be used to identify rare alleles responsible for hereditary hearing loss: 22 of the 30 (73.3%) genes identified with mutations are rarely mutated in hereditary hearing loss and only account for 21.5% (42/195) of the total mutation frequency, explaining no more than 2% for each gene. These rarely mutated genes would be missed by conventional diagnostic sequencing approaches. Conclusions: NGS can be used effectively to identify both the common and rare genes causing hereditary hearing loss.