Mutation in the zonadhesin-like domain of α-tectorin associated with autosomal dominant non-syndromic hearing loss
Mutation in the zonadhesin-like domain of α-tectorin associated with autosomal dominant non-syndromic hearing loss
复制标题
DOI：
10.1038/sj.ejhg.5200273
复制
发表时间：
1999-02-01
影响因子：
5.2
通讯作者：
Lina-Granade, G
中科院分区：
文献类型：
--
作者：
Alloisio, N;Morlé, L;Lina-Granade, G
一个基因负责常染色体显性遗传的非综合征性听力障碍的两个家庭（DFNA 8和DFNA 12）最近被确定为TECTA编码α-tectorin，一个主要组成部分的顶盖膜。在这些家族中，α-tectorin的透明质酸结构域内的错义突变与稳定的严重中频听力损失相关。本研究报告了一个新的常染色体显性高频听力损失家族中与DFNA 12的联系，该家族的严重程度从轻度进展到中度。在Zonadhesin样结构域中发现了一个错义突变（C1619 S），该突变消除了D4 von Willebrand因子（vWf）D型重复序列中的第一个相邻半胱氨酸（（1619）Cys-Gly-Leu-（1622）Cys）。这些结果进一步支持TECTA突变参与常染色体显性遗传性听力障碍，并表明，邻近的半胱氨酸参与覆膜基质组装。
A gene responsible for autosomal dominant non-syndromic hearing impairment in two families (DFNA8 and DFNA12) has recently been identified as TECTA encoding alpha-tectorin, a major component of the tectorial membrane. In these families, missense mutations within the zona pellucida domain of alpha-tectorin were associated with stable severe mid-frequency hearing loss, The present study reports linkage to DFNA12 in a new family with autosomal dominant high frequency hearing loss progressing from mild to moderate severity. The candidate region refined to 3.8 cM still contained the TECTA gene, A missense mutation (C1619S) was identified in the zonadhesin-like domain, This mutation abolishes the first of the vicinal cysteines ((1619)Cys-Gly-Leu-(1622)Cys) present in the D4 von Willebrand factor (vWf) type D repeat. These results further support the involvement of TECTA mutations in autosomal dominant hearing impairment, and suggest that vicinal cysteines are involved in tectorial membrane matrix assembly.