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线粒体12S rRNA A1555G突变是引起氨基糖甙类药物诱导的非综合征型耳聋的重要原因之一。文章对收集的25个携带A1555G突变的中国汉族非综合征型耳聋家系进行了临床和分子遗传学评估。结果表明,这25个家系的母系成员在耳聋外显率、听力损失严重程度和发病年龄上存在较大差异。当包括和不包括氨基糖甙类药物使用史时,耳聋的平均外显率分别为28.1%和21.5%,排除氨基糖甙类药物时,耳聋的平均发病年龄从1~15岁不等。线粒体全序列分析发现了16个新变异,不同的线粒体DNA多态性位点显示这25个家系分别属于东亚人群A、B、D、F、G、M、N和R单倍型,其中线粒体单倍型B的家系耳聋外显率和表现度较其他单倍型高。此外,7个继发突变位点和21个高保守性位点突变可能增加了这些家系的耳聋外显率。GJB2基因上未检测到与耳聋相关的突变,表明在本研究的耳聋家系中,GJB2基因可能没有参与A1555G突变的表型表达。以上各方面提示,线粒体单倍型和其他因素可能参与了这25个家系耳聋患者的表型修饰。
Mitochondrial 12S rRNA A1555G mutation is caused by aminoglycoside-induced non-syndromic deafness one of the important reasons. The clinical and molecular genetic evaluation of 25 Han Chinese non-syndromic deafness families carrying the A1555G mutation was evaluated. The results showed that the maternal members of these 25 pedigrees had significant differences in penetrating deafness, severity of hearing loss and age of onset. The mean penetrances of deafness were 28.1% and 21.5%, respectively, with and without the aminoglycoside use history. Excluding aminoglycosides, the mean age at onset of deafness ranged from 1 to 15 years. A total of 16 new mutations were found in mitochondrial genome. Different mitochondrial DNA polymorphisms showed that these 25 families belong to A, B, D, F, G, M, N and R haplotypes respectively in East Asian population. Mitochondrial Haplotype B family deafness penetrance and performance than other haplotypes. In addition, mutations in seven secondary and 21 highly conserved sites may increase the deafness penetrance in these families. No mutations associated with deafness were detected in the GJB2 gene, indicating that the GJB2 gene may not be involved in the phenotypic expression of the A1555G mutation in the deaf-off pedigrees of this study. The above aspects suggest that mitochondrial haplotype and other factors may be involved in the phenotypic modification of deafness in these 25 families.