Targeted Next-Generation Sequencing in Uyghur Families with Non-Syndromic Sensorineural Hearing Loss

The mutation spectrum of deafness genes may vary in different ethnical groups. In this study, we investigated the genetic etiology of nonsyndromic deafness in four consanguineous and two multiplex Uyghur families in which mutations in common deafness genes GJB2, SLC26A4 and MT-RNR1 were excluded. Targeted next-generation sequencing of 97 deafness genes was performed in the probands of each family. Novel pathogenic mutations were identified in four probands including the p.L416R/p.A438T compound heterozygous mutations in TMC1, the homozygous p.V1880E mutation in MYO7A, c.1238delT frameshifting deletion in PCDH15 and c.9690+1G>A splice site mutation in MYO15A. Co-segregation of the mutations and the deafness were confirmed within each family by Sanger sequencing. No pathogenic mutations were identified in one multiplex family and one consanguineous family. Our study provided a useful piece of information for the genetic etiology of deafness in Uyghurs.不同族群的耳聋基因突变谱可能存在差异。本研究针对4个近亲婚配家系与2个多发维吾尔族家系的非综合征性耳聋（nonsyndromic deafness）开展遗传病因学探究，上述家系已排除常见耳聋基因GJB2、SLC26A4及MT-RNR1的突变。研究对每个家系的先证者开展97个耳聋基因的靶向下一代测序（targeted next-generation sequencing），在4名先证者中鉴定出新型致病性突变，包括TMC1基因的p.L416R/p.A438T复合杂合突变、MYO7A基因的纯合p.V1880E突变、PCDH15基因的c.1238delT移码缺失突变，以及MYO15A基因的c.9690+1G>A剪接位点突变。通过Sanger测序（Sanger sequencing）验证了各家系中突变与耳聋表型的共分离关系。另有1个多发家系与1个近亲婚配家系未检出致病性突变。本研究为维吾尔族人群耳聋的遗传病因学研究提供了有价值的参考依据。