We report three possibly disease-causing point mutations in one of the inner-ear-specific genes, KIAA1199. We identified an R187C mutation in one family, an R187H mutation in two unrelated families, and an H783Y mutation in one sporadic case of nonsyndromic hearing loss. In situ hybridization indicated that the murine homolog of KIAA1199 mRNA is expressed specifically in Deiters' cells in the organ of Corti at postnatal day zero (P n) P0 before the onset of hearing, but expression in those cells disappears by day P7. The signal of KIAA1199 was also observed in fibrocytes of the spiral ligament and the spiral limbus through to P21, when the murine cochlea matures. Thus, the gene product may be involved in uptake of potassium ions or trophic factors with a particular role in auditory development. Although the R187C and R187H mutations did not appear to affect subcellular localization of the gene product in vitro, the H783Y mutation did present an unusual cytoplasmic distribution pattern that could underlie the molecular mechanism of hearing impairment. Our data bring attention to a novel candidate for hearing loss and indicate that screening of mutations in inner-ear-specific genes is likely to be an efficient approach to finding genetic elements responsible for deafness.

中文翻译：

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编码KIAA1199蛋白（在Deiters细胞和纤维细胞中表达的内耳蛋白）的基因中的突变，是导致非综合征性听力损失的原因。

我们报告内耳特异性基因之一，KIAA1199中的三个可能引起疾病的点突变。我们确定了一个家族中的一个R187C突变，两个不相关家族中的一个R187H突变，以及一例非综合征性听力损失的偶发病例中的H783Y突变。原位杂交表明，KIAA1199 mRNA的鼠类同源物在听力开始前的出生后第零天（P n）P0在Corti器官的Deiters'细胞中特异性表达，但在第7天消失。当鼠耳蜗成熟时，在螺旋韧带和螺旋角膜缘直至P21的纤维细胞中也观察到了KIAA1199的信号。因此，基因产物可能参与钾离子或营养因子的摄取，在听觉发育中起特定作用。尽管R187C和R187H突变似乎并未影响体外基因产物的亚细胞定位，但H783Y突变确实表现出异常的细胞质分布模式，这可能是听力障碍的分子机制的基础。我们的数据使人们注意到了一种新型的听力损失候选者，并表明筛选内耳特异性基因的突变很可能是寻找导致耳聋的遗传因素的有效方法。