Clinical and genetic study of 12 Chinese Han families with nonsyndromic deafness
Clinical and genetic study of 12 Chinese Han families with nonsyndromic deafness
复制标题
12个汉族非综合征性耳聋家系的临床及遗传学研究
DOI：
10.1002/mgg3.1177
复制
发表时间：
2020-02-12
影响因子：
2
通讯作者：
Zhang, Luping
中科院分区：
文献类型：
--
作者：
Wu, Di;Huang, Weiyuan;Zhang, Luping
背景：非综合征性听力损失具有临床和遗传异质性。在这项研究中，我们对12个中国汉族耳聋家庭的临床特征进行了分析，其中排除了常见耳聋基因GJB2、SLC26A4和MT-RNR1的突变。方法对10个家族的先证进行147个已知聋基因的新一代靶向测序，对其余2个家族的先证进行全外显子组测序。结果12个先证中共鉴定出OTOF、CDH23、PCDH15、PDZD7、ADGRV1、KARS、OTOG、GRXCR2、MYO6、GRHL2、POU3F4等11个罕见耳聋基因的致病突变，其中16个为新突变。Sanger测序证实了突变和耳聋表型的家族内共分离。结论本研究扩大了中国汉族非综合征性听力损失的突变谱和基因型-表型相关性，并强调了将下一代测序和详细听觉评估相结合对实现更准确的非综合征性听力损失诊断的重要性。
Background Nonsyndromic hearing loss is clinically and genetically heterogeneous. In this study, we characterized the clinical features of 12 Chinese Han deaf families in which mutations in common deafness genes GJB2, SLC26A4, and MT-RNR1 were excluded.Methods Targeted next-generation sequencing of 147 known deafness genes was performed in probands of 10 families, while whole-exome sequencing was applied in those of the rest two.Results Pathogenic mutations in a total of 11 rare deafness genes, OTOF, CDH23, PCDH15, PDZD7, ADGRV1, KARS, OTOG, GRXCR2, MYO6, GRHL2, and POU3F4, were identified in all 12 probands, with 16 mutations being novel. Intrafamilial cosegregation of the mutations and the deafness phenotype were confirmed by Sanger sequencing.Conclusion Our results expanded the mutation spectrum and genotype-phenotype correlation of nonsyndromic hearing loss in Chinese Hans and also emphasized the importance of combining both next-generation sequencing and detailed auditory evaluation to achieve a more accurate diagnosis for nonsyndromic hearing loss.