Identification of I411K, a novel missense EYA4 mutation causing autosomal dominant non-syndromic hearing loss
Identification of I411K, a novel missense EYA4 mutation causing autosomal dominant non-syndromic hearing loss
复制标题
I411K 的鉴定，这是一种导致常染色体显性非综合征性听力损失的新型错义 EYA4 突变
DOI：
10.3892/ijmm.2014.1939
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发表时间：
2014-12-01
影响因子：
5.4
通讯作者：
Xing, Guangqian
中科院分区：
文献类型：
--
作者：
Tan, Minxing;Shen, Xiaofei;Xing, Guangqian
听力损失是人类最常见的感觉缺陷，更好地了解其潜在原因对于改善咨询和康复是必要的。本研究对中国一个常染色体显性非综合征进行性听力障碍家庭进行了遗传分析和评估。全外显子组测序结合共分离分析在EYA4外显子15上发现了一个新的错义突变（c.T1301A; p.I411K）。这种突变伴随着家族成员的听力丧失而分离。该突变未在1000基因组计划、dbSNP 130、HapMap和YH计划数据库中发现，也未在匹配对照中发现。生物信息学分析证实了该突变的致病作用。据我们所知，这是第一份描述导致非综合征性听力损失的EYA4基因错义突变的报告。我们的研究结果提供了额外的分子和临床信息，以便更好地了解EYA4突变的发病机制和DFNA10听力损失的基因型-表型相关性。
Hearing loss is the most common sensory deficit in humans and gaining a better understanding of the underlying causes is necessary to improve counseling and rehabilitation. In the present study, a genetic analysis of a Chinese family with autosomal dominant non-syndromic progressive hearing impairment was conducted and assessed. Whole-exome sequencing in combination with a co-segregation analysis identified a novel missense mutation in EYA4 exon 15 (c.T1301A; p.I411K). The mutation segregated with the hearing loss of the family. This mutation was not identified in the databases of 1000 Genome Project, dbSNP 130, HapMap and YH project or in matched controls. Bioinformatic analysis confirmed the pathogenic effects of this mutation. To the best of our knowledge, this is the first report to provide a description of a missense mutation in the EYA4 gene resulting in non-syndromic hearing loss. Our results provide additional molecular and clinical information in order to gain improved understanding of the pathogenesis of EYA4 mutations and the genotype-phenotype correlations of DFNA10 hearing loss.