Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous
Nonsyndromic deafness DFNA1 associated with mutation of a human homolog of the Drosophila gene diaphanous
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DOI：
10.1126/science.278.5341.1315
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发表时间：
1997-11-14
期刊：
影响因子：
56.9
通讯作者：
King, MC
中科院分区：
文献类型：
--
作者：
Lynch, ED;Lee, MK;King, MC
在哥斯达黎加的一个大家族中，负责常染色体显性、完全渗透、非综合征型感音神经性进行性听力损失的基因先前定位于染色体5q31，并命名为DFNA 1。该家族的耳聋与果蝇基因透明的人类同源物中的蛋白质截短突变有关。截短是由剪接供体中的单核苷酸取代引起的，导致信使RNA中的四个碱基对插入和移码。透明蛋白是一种profilin配体和Rho的靶点，调节肌动蛋白的聚合，肌动蛋白是肌动蛋白的主要组成部分。内耳毛细胞骨架。
The gene responsible for autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive hearing loss in a large Costa Rican kindred was previously localized to chromosome 5q31 and named DFNA1. Deafness in the family is associated with a protein-truncating mutation in a human homolog of the Drosophila gene diaphanous. The truncation is caused by a single nucleotide substitution in a splice donor, leading to a four-base pair insertion in messenger RNA and a frameshift, The diaphanous protein is a profilin ligand and target of Rho that regulates polymerization of actin, the major component of the cytoskeleton of hair cells of the inner ear.