A novel splice site mutation in EYA4 causes DFNA10 hearing loss
A novel splice site mutation in EYA4 causes DFNA10 hearing loss
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DOI：
10.1002/ajmg.a.31860
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发表时间：
2007-07-15
影响因子：
2
通讯作者：
Dahl, Hans-Henrik M.
中科院分区：
文献类型：
--
作者：
Hildebrand, Michael S.;Coman, David;Dahl, Hans-Henrik M.
2001 年，在两个家族中描述了 DFNA10 位点的非综合征型显性感音神经性听力损失 (SNHL)。确定了影响眼睛缺失 4' (EYA4) 蛋白 EyaHR 结构域的致病突变。我们报告了一个患有非综合征性 SNHL 的澳大利亚家庭的临床和遗传分析。 EYA4基因的筛选显示出新的多嘧啶束变异约。 1282-12T > A，引入新的 3' 剪接受体位点。这是关于 EYA4 点突变的第一份报告，该突变被假设会导致异常的前 mRNA 剪接和人类疾病。所描述的 DFNA10 家族只是第四个已确定的家族。其中一名个体表现出与其他受影响的家庭成员明显相同的表型。然而，基因分型表明他不具有 DFNA10 疾病单倍型。详细的临床调查显示，他的听力损失的发作和严重程度存在差异，因此推测他代表了表型，可能是由于长期暴露在大声噪音中造成的。 (C) 2007 Wiley-Liss, Inc.
Nonsyndromic antosomal dominant sensorineural hearing loss (SNHL) at the DFNA10 locus was described in two families in 2001. Causative mutations that affect the EyaHR domain of the Eyes absent 4' (EYA4) protein were identified. We report on the clinical and genetic analyses of an Australian family with nonsyndromic SNHL. Screening of the EYA4 gene showed the novel polypyrimidine tract variation ca. 1282-12T > A that introduces a new 3' splice acceptor site. This is the first report of a point mutation in EYA4 that is hypothesized to lead to aberrant pre-mRNA splicing and human disease. The DFNA10 family described is only the fourth to be identified. One individual presented with apparently the same phenotype as other affected members of the family. However, genotyping illustrated that he did not share the DFNA10 disease haplotype. Detailed clinical investigation showed differences in the onset and severity of his hearing loss and thus he is presumed to represent a phenocopy, perhaps resulting from long-term exposure to loud noise. (C) 2007 Wiley-Liss, Inc.