DFNA1 IN INHERITED HEARING LOSS

产品说明： 研究人员研究了一个哥斯达黎加常染色体 显性进行性非综合征性听力损失（DFNA 1），最近 通过定位克隆鉴定了一个蛋白质截短突变， 果蝇透明基因的人类同源物。 这种突变是在 在所有耳聋家庭成员中，而在正常听力家庭成员中， 300个对照个体。 此应用程序的目标是 (1)为该突变的致病性提供功能支持 a）通过同源重组产生突变小鼠， 显示这些小鼠突变体具有耳聋表型（特异性目的1 和3）和B）证明蛋白质异常导致异常 稳定性或细胞内定位（具体目标2和4），（2） 开始研究与透明蛋白相互作用的蛋白质， 并为其他致聋基因提供候选基因 （具体目标5）， (3)研究其他三个耳聋家族，以确定新的耳聋。 耳聋基因（具体目标6）;（4）收集200名耳聋个体 与凯撒永久系统的一些家庭成员一起担任将军 资源，并筛选他们的突变，在透明系统（具体 目标7）。

DESCRIPTION: The investigators have studied a large Costa Rican family with autosomal dominant progressive non-syndromic hearing loss (DFNA1), and have recently through positional cloning identified a protein truncation mutation in the human homologue of the Drosophila diaphanous gene. This mutation was found in all deaf family members, and not in normal hearing family members or over 300 control individuals. The goals of this application are (1) to provide functional support for the pathogenicity of this mutation through a) generating mutant mice through homologous recombination and showing that these mouse mutants have a deafness phenotype (specific aims 1 and 3) and b) demonstrating that the protein abnormality leads to abnormal stability or intracellular localization (specific aims 2 and 4), (2) to start the study of proteins interacting with diaphanous which will elucidate the pathogenic pathway and provide candidate genes for other deafness genes (specific aim 5), (3) to study three other deafness families toward the identification of new deafness genes (specific aim 6), and (4) to collect 200 deaf individuals with some family members from the Kaiser Permanente system as a general resource, and screen them for mutations in the diaphanous system (specific aim 7).