Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F
Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F
复制标题
DOI：
10.1093/hmg/10.16.1709
复制
发表时间：
2001-08-01
影响因子：
3.5
通讯作者：
Smith, RJH
中科院分区：
文献类型：
--
作者：
Alagramam, KN;Yuan, HJ;Smith, RJH
我们已经确定了分子基础的Usher综合征1F型（USH 1F）在两个家庭分离这种类型的综合征性耳聋。通过荧光原位杂交，我们将小鼠原钙粘蛋白Pcdh 15的人类同源物放置在由USH 1F位点定义的连锁区间中。我们确定了这种新的原钙粘蛋白的基因组结构，并发现一个USH 1F家族的外显子10的单碱基缺失和第二个外显子2的无义突变。与在这些家族中观察到的表型一致，我们通过RT-PCR和免疫组织化学证实了PCDH 15在视网膜和耳蜗中的表达。本报告表明，原钙粘蛋白是维持正常的视网膜和耳蜗功能所必需的。
We have determined the molecular basis for Usher syndrome type 1F (USH1F) in two families segregating for this type of syndromic deafness. By fluorescence in situ hybridization, we placed the human homolog of the mouse protocadherin Pcdh15 in the linkage interval defined by the USH1F locus. We determined the genomic structure of this novel protocadherin, and found a single-base deletion in exon 10 in one USH1F family and a nonsense mutation in exon 2 in the second. Consistent with the phenotypes observed in these families, we demonstrated expression of PCDH15 in the retina and cochlea by RT-PCR and immunohistochemistry. This report shows that protocadherins are essential for maintenance of normal retinal and cochlear function.