Data_Sheet_1_Molecular etiology study of hearing loss in 13 Chinese Han families.docx

Hearing loss affecting about 2/1000 newborns is the most common congenital disease. Genetic defects caused approximately 70% of patients who have non-syndromic hearing loss. We recruited 13 Chinese Han deafness families who tested negative for GJB2, SLC26A4, and mitochondrial 12S rRNA. The probands of each family were performed whole-exome sequencing (WES) or targeted next-generation sequencing (NGS) for known deafness genes to study for pathogenic causes. We found four novel mutations of CDH23, one novel mutation of MYO15A, one novel mutation of TMC1, one novel mutation of PAX3, and one novel mutation of ADGRV1, one novel CNV of ADGRV1, and one novel CNV of STRC. Hearing loss is a highly hereditary and heterogeneous disease. The results in the limited samples of this study show that Usher and Waardenburg syndrome-related genes account for a major proportion are strongly associated with Chinese Han hearing loss patients negative for GJB2, SLC26A4, and mitochondrial 12S rRNA, followed by STRC resulting in mild to moderate deafness.

新生儿听力损失发病率约为2‰，是最常见的先天性疾病。约70%的非综合征性听力损失患者的病因与遗传缺陷相关。本研究纳入13个中国汉族耳聋家系，所有家系的样本经GJB2、SLC26A4及线粒体12S rRNA基因检测均呈阴性。针对每个家系的先证者，我们采用全外显子组测序（whole-exome sequencing, WES）或靶向下一代测序（targeted next-generation sequencing, NGS）对已知耳聋相关基因进行检测，以明确其致病病因。本研究共发现CDH23的4个全新突变位点，MYO15A、TMC1、PAX3、ADGRV1各1个全新突变位点，另发现ADGRV1和STRC各1个全新拷贝数变异（copy number variation, CNV）。听力损失是一种具有高度遗传异质性的疾病。本研究基于有限样本量所得结果显示，针对GJB2、SLC26A4及线粒体12S rRNA基因检测阴性的中国汉族听力损失患者，乌谢尔综合征与瓦登伯革综合征相关致病基因占主要病因比例，且与该类患者显著相关；其次为导致轻中度听力损失的STRC基因变异。