Whole-exome sequencing identifies rare pathogenic and candidate variants in sporadic Chinese Han deaf patients
Whole-exome sequencing identifies rare pathogenic and candidate variants in sporadic Chinese Han deaf patients
复制标题
全外显子组测序鉴定出中国汉族散发性耳聋患者的罕见致病变异和候选变异
DOI：
10.1111/cge.13638
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发表时间：
2020-02-01
影响因子：
3.5
通讯作者：
Hu, Hongyi
中科院分区：
文献类型：
--
作者：
Zou, Songfeng;Mei, Xueshuang;Hu, Hongyi
听力损失的遗传原因是高度异质性的，通常具有种族特异性。近年来，已经开发了多种下一代测序（NGS）面板以靶向致病基因。另一方面，全外显子组测序（WES）很少用于耳聋的基因检测。在这项研究中，我们对38例散发性中国汉族耳聋患者进行了WES，这些患者预先排除了常见耳聋基因GJB 2，SLC 26 A4和MT-RNR 1的突变。非同义变体已根据其在公共数据库和种族匹配对照中的次要等位基因频率进行过滤。在10例患者中发现了OTOF、TRIOBP、ESPN、HARS 2、CDH 23、MYO 7A、USH 1C和TJP 2 8个耳聋基因的双等位基因致病突变，其中17个突变与既往耳聋无关。对于其余28例患者，可能的双等位基因罕见的非同义变异，平均每例患者4.7个基因被确定为候选致病原因，以供将来分析。我们的研究表明，WES可以为耳聋的基因检测提供一个统一的平台，并在发现新的致病基因时进行追溯分析。
Genetic causes of hearing loss are highly heterogeneous and often ethnically specific. In recent years, a variety of next-generation sequencing (NGS) panels have been developed to target deafness-causative genes. Whole-exome sequencing (WES), on the other hand, was rarely used for genetic testing for deafness. In this study, we performed WES in 38 sporadic Chinese Han deaf patients who have been pre-excluded for mutations in common deafness genes GJB2, SLC26A4 and MT-RNR1. Non-synonymous variants have been filtered based on their minor allele frequencies in public databases and ethnically matched controls. Bi-allelic pathogenic mutations in eight deafness genes, OTOF, TRIOBP, ESPN, HARS2, CDH23, MYO7A, USH1C and TJP2, were identified in 10 patients, with 17 mutations identified in this study not being associated with deafness previously. For the rest 28 patients, possibly bi-allelic rare non-synonymous variants in an averaged 4.7 genes per patient were identified as candidate pathogenic causes for future analysis. Our study showed that WES may provide a unified platform for genetic testing of deafness and enables retro-analyzing when new causative genes are revealed.