Identification of a Novel MYO15A Mutation in a Chinese Family with Autosomal Recessive Nonsyndromic Hearing Loss.
Identification of a Novel MYO15A Mutation in a Chinese Family with Autosomal Recessive Nonsyndromic Hearing Loss.
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DOI：
10.1371/journal.pone.0136306
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Deng H
中科院分区：
文献类型：
--
作者：
Xia H;Huang X;Guo Y;Hu P;He G;Deng X;Xu H;Yang Z;Deng H
常染色体隐性遗传性非综合征性听力损失（ARNSHL）是一种遗传异质性感音神经性疾病，通常表现为语前听力损失，无其他临床表现。本研究的目的是鉴定一个四代同源的中国人ARNSHL家系的致病基因。通过外显子组测序和桑格测序鉴定了myoxin XVa基因（MYO 15 A）的一个新的纯合变异体c.9316dupC（p.H3106Pfs*2）。纯合子MYO 15 A c.9316dupC变异体与ARNSHL家族中的表型共分离，并且在200名正常对照中不存在。预测该变体干扰静纤毛尖端的肌球蛋白XVa-旋转蛋白-Eps 8复合物的形成，这对于静纤毛伸长是必不可少的。我们的数据表明，纯合MYO 15 A c.9316dupC变异可能是致病性突变，外显子组测序是一个强大的分子诊断策略ARNSHL，一个非常异质性的疾病。我们的研究结果扩展了MYO 15 A基因的突变谱，对家庭遗传咨询具有重要意义。
Autosomal recessive nonsyndromic hearing loss (ARNSHL) is a genetically heterogeneous sensorineural disorder, generally manifested with prelingual hearing loss and absence of other clinical manifestations. The aim of this study is to identify the pathogenic gene in a four-generation consanguineous Chinese family with ARNSHL. A novel homozygous variant, c.9316dupC (p.H3106Pfs*2), in the myoxin XVa gene (MYO15A) was identified by exome sequencing and Sanger sequencing. The homozygous MYO15A c.9316dupC variant co-segregated with the phenotypes in the ARNSHL family and was absent in two hundred normal controls. The variant was predicted to interfere with the formation of the Myosin XVa-whirlin-Eps8 complex at the tip of stereocilia, which is indispensable for stereocilia elongation. Our data suggest that the homozygous MYO15A c.9316dupC variant might be the pathogenic mutation, and exome sequencing is a powerful molecular diagnostic strategy for ARNSHL, an extremely heterogeneous disorder. Our findings extend the mutation spectrum of the MYO15A gene and have important implications for genetic counseling for the family.