Ahmed Zubair M, Riazuddin Saima, Ahmad Jamil, Bernstein Steve L, Guo Yan, Sabar Muhammad F, Sieving Paul, Riazuddin Sheikh, Griffith Andrew J, Friedman Thomas B, Belyantseva Inna A, Wilcox Edward R
Section of Human Genetics, Laboratory of Molecular Genetics, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD, USA.
Hum Mol Genet. 2003 Dec 15;12(24):3215-23. doi: 10.1093/hmg/ddg358. Epub 2003 Oct 21.
Recessive splice site and nonsense mutations of PCDH15, encoding protocadherin 15, are known to cause deafness and retinitis pigmentosa in Usher syndrome type 1F (USH1F). Here we report that non-syndromic recessive hearing loss (DFNB23) is caused by missense mutations of PCDH15. This suggests a genotype-phenotype correlation in which hypomorphic alleles cause non-syndromic hearing loss, while more severe mutations of this gene result in USH1F. We localized protocadherin 15 to inner ear hair cell stereocilia, and to retinal photoreceptors by immunocytochemistry. Our results further strengthen the importance of protocadherin 15 in the morphogenesis and cohesion of stereocilia bundles and retinal photoreceptor cell maintenance or function.
已知编码原钙黏蛋白15的PCDH15的隐性剪接位点和无义突变会导致1F型Usher综合征（USH1F）中的耳聋和色素性视网膜炎。在此我们报告，非综合征性隐性听力损失（DFNB23）是由PCDH15的错义突变引起的。这表明存在一种基因型-表型相关性，即亚效等位基因导致非综合征性听力损失，而该基因更严重的突变则导致USH1F。我们通过免疫细胞化学将原钙黏蛋白15定位到内耳毛细胞静纤毛以及视网膜光感受器。我们的结果进一步强化了原钙黏蛋白15在静纤毛束的形态发生和黏附以及视网膜光感受器细胞维持或功能中的重要性。
