对摩洛哥非综合征性听力损失家系中 TMPRSS3 基因的分子分析。

Molecular analysis of the TMPRSS3 gene in Moroccan families with non-syndromic hearing loss.

机构信息

Laboratoire de Génétique Moléculaire et Humaine, Département de Recherche Scientifique, Institut Pasteur du Maroc, 20360 Casablanca, Morocco.

出版信息

Biochem Biophys Res Commun. 2012 Mar 23;419(4):643-7. doi: 10.1016/j.bbrc.2012.02.066. Epub 2012 Feb 20.

Abstract

Autosomal recessive non-syndromic hearing impairment (ARNSHI) is the most common type of inherited hearing impairment, accounting for approximately 80% of inherited prelingual hearing impairment. Hearing loss is noted to be both phenotypically and genetically heterogeneous. Mutations in the TMPRSS3 gene, which encodes a transmembrane serine protease, are known to cause autosomal recessive non-syndromic hearing impairment DFNB8/10. In order to elucidate if the TMPRSS3 gene is responsible for ARNSHI in 80 Moroccan families with non-syndromic hearing impairment, the gene was sequenced using DNA samples from these families. Nineteen TMPRSS3 variants were found, nine are located in the exons among which six are missense and three are synonymous. The 10 remaining variations are located in non-coding regions. Missense variants analysis show that they do not have a significant pathogenic effect on protein while pathogenicity of some variant remains under discussion. Thus we show that the TMPRSS3 gene is not a major contributor to non-syndromic deafness in the Moroccan population.

摘要

常染色体隐性非综合征型听力损失(ARNSHI)是最常见的遗传性听力损失类型,约占遗传性语前听力损失的 80%。听力损失在表型和遗传上均具有异质性。已知编码跨膜丝氨酸蛋白酶的 TMPRSS3 基因突变可导致常染色体隐性非综合征型听力损失 DFNB8/10。为了阐明 TMPRSS3 基因是否与 80 个摩洛哥非综合征型听力损失家系的 ARNSHI 有关,我们对这些家系的 DNA 样本进行了基因测序。共发现 19 种 TMPRSS3 变异,其中 9 种位于外显子中,其中 6 种为错义突变,3 种为同义突变。其余 10 种变异位于非编码区。错义变异分析表明,它们对蛋白质没有显著的致病作用,而一些变异的致病性仍在讨论中。因此,我们表明 TMPRSS3 基因不是摩洛哥人群中非综合征性耳聋的主要致病基因。

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