Analysis on genetic factors specific to Japanese population in deafness due to mitochondrial mutations.

目前还没有研究日本耳聋患者线粒体DNA中耳聋相关突变的患病率。为了澄清这个问题，我们着手分析了53名先天性听力损失受试者、76名迟发性听力损失受试者和144名听力正常受试者的线粒体DNA中的耳聋基因。在对同源性突变的分析中，在53名先天性听力损失受试者中的8名和76名迟发性听力损失受试者中的4名中检测到在国际数据库中已报告与耳聋相关的突变。在异质性突变分析中，在53例先天性耳聋和76例迟发性耳聋中分别有7例和7例检测到耳聋相关突变。在听力正常对照组中，11例12SrRNA基因发生耳聋相关突变，其余4个基因均未发生耳聋相关突变。这些结果表明，除了线粒体DNA突变外，环境因素也参与了日本人群听力损失的发生，或者这些突变在该人群中不是致病性的。因此，在国际数据库和日本人群中，与听力损失相关的线粒体遗传因素似乎存在显著差异。本研究报告的数据可供进一步阐明日本人群耳聋的遗传因素以及耳聋诊断中的基因检测参考。

There has been no study on the prevalence of deafness related mutations in the mitochondrial DNA as a whole in Japanese deaf patients. In order to clarify this question, we set out to analyze deafness genes in the mitochondrial DNA in 53 subjects with congenital hearing loss, 76 subjects with late-onset hearing loss, and 144 subjects with normal hearing. In the analysis on homoplasmy mutations, mutations which have been reported to be associated with deafness in the international data base were detected in 8 of 53 subjects with congenital hearing loss and 4 of 76 subjects with late-onset hearing loss. In the analysis on heteroplasmy mutations, deafness related mutations were detected in 7 of 53 subjects with congenital hearing loss and 7 of 76 subjects with late-onset hearing loss. In the analysis on normal hearing controls, 11 of 144 subjects had deafness related mutations in 12S rRNA gene and none of 144 subjects had deafness related mutations in the other 4 genes. These results indicate that environmental factors are involved in the occurrence of hearing loss in addition to mutations in the mitochondrial DNA in Japanese population or these mutations are not pathogenic in this population. Therefore, there seems to be significant difference in mitochondrial genetic factors associated with hearing loss in the international data base and those in Japanese population. The data reported in this study should be consulted for further clarification of genetic factors involved in the deafness in Japanese population as well as for the genetic testing in the diagnosis of deafness.