de Kok Y J, van der Maarel S M, Bitner-Glindzicz M, Huber I, Monaco A P, Malcolm S, Pembrey M E, Ropers H H, Cremers F P
Department of Human Genetics, University Hospital Nijmegen, Netherlands.
Science. 1995 Feb 3;267(5198):685-8. doi: 10.1126/science.7839145.
Deafness with fixation of the stapes (DFN3) is the most frequent X-linked form of hearing impairment. The underlying gene has been localized to a 500-kilobase segment of the Xq21 band. Here, it is reported that a candidate gene for this disorder, Brain 4 (POU3F4), which encodes a transcription factor with a POU domain, maps to the same interval. In five unrelated patients with DFN3 but not in 50 normal controls, small mutations were found that result in truncation of the predicted protein or in nonconservative amino acid substitutions. These findings indicate that POU3F4 mutations are a molecular cause of DFN3.
镫骨固定性耳聋（DFN3）是最常见的X连锁型听力障碍。相关致病基因已定位到Xq21带的一个500千碱基片段上。本文报道，该疾病的一个候选基因——脑4（POU3F4），它编码一种具有POU结构域的转录因子，也定位于同一区间。在5例无亲缘关系的DFN3患者中发现了小的突变，而在50名正常对照中未发现，这些突变导致预测蛋白的截短或非保守氨基酸替换。这些发现表明，POU3F4突变是DFN3的分子病因。
