12 个中国汉族非综合征性耳聋家系的临床和遗传学研究。
Clinical and genetic study of 12 Chinese Han families with nonsyndromic deafness.
机构信息
Department of Otolaryngology, Affiliated Hospital of Nantong University, Nantong, China.
Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, China.
出版信息
Mol Genet Genomic Med. 2020 Apr;8(4):e1177. doi: 10.1002/mgg3.1177. Epub 2020 Feb 12.
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.
背景
非综合征性听力损失在临床上和遗传上具有异质性。在这项研究中，我们对排除了常见耳聋基因 GJB2、SLC26A4 和 MT-RNR1 突变的 12 个汉族耳聋家系的临床特征进行了描述。
方法
对 10 个家系的先证者进行了 147 个已知耳聋基因的靶向下一代测序，而对其余 2 个家系的先证者则进行了全外显子组测序。
结果
在所有 12 个先证者中均发现了总共 11 个罕见耳聋基因（OTOF、CDH23、PCDH15、PDZD7、ADGRV1、KARS、OTOG、GRXCR2、MYO6、GRHL2 和 POU3F4）的致病性突变，其中 16 个突变为新发现。通过 Sanger 测序证实了突变与耳聋表型的家系内共分离。
结论
我们的研究结果扩展了中国汉族人群非综合征性听力损失的突变谱和基因型-表型相关性，并强调了结合下一代测序和详细的听觉评估以实现更准确的非综合征性听力损失诊断的重要性。
Zotero 插件