Hildebrand Michael S, Coman David, Yang Tao, Gardner R J McKinlay, Rose Elizabeth, Smith Richard J H, Bahlo Melanie, Dahl Hans-Henrik M
Department of Otolaryngology--Head and Neck Surgery, University of Iowa, Iowa City, Iowa 52242, USA.
Am J Med Genet A. 2007 Jul 15;143A(14):1599-604. doi: 10.1002/ajmg.a.31860.
Nonsyndromic autosomal 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. 1,282-12T > 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.
2001年，在两个家族中发现了位于DFNA10位点的非综合征性常染色体显性遗传性感音神经性听力损失（SNHL）。已确定影响“无眼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的澳大利亚家族的临床和基因分析。对EYA4基因的筛查显示了新的多嘧啶序列变异，约1282 - 12T>A，该变异引入了一个新的3'剪接受体位点。这是关于EYA4基因点突变的首次报道，据推测该突变会导致异常的前体mRNA剪接并引发人类疾病。所描述的DFNA10家族是第四个被鉴定出来的家族。有一个个体表现出与该家族其他受影响成员明显相同的表型。然而，基因分型表明他并不共享DFNA10疾病单倍型。详细的临床调查显示他的听力损失在发病时间和严重程度上存在差异，因此推测他代表一种表型模拟，可能是长期暴露于噪音所致。
