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

目前还没有关于日本聋人线粒体DNA中与耳聋相关的突变的整体流行率的研究。为了澄清这一问题，我们开始分析53名先天性听力损失患者、76名晚发型听力损失患者和144名正常听力患者线粒体DNA中的耳聋基因。在同源突变分析中，53例先天性听力损失患者中有8例检测到国际数据库中报道的与耳聋相关的突变，76例晚发性听力损失患者中有4例检测到突变。在异质性突变分析中，53例先天性听力损失患者中有7例检测到耳聋相关突变，76例晚发型听力损失患者中有7例检测到耳聋相关突变。在正常听力对照分析中，144例受试者中有11例12S rRNA基因出现耳聋相关突变，其余4个基因均未出现耳聋相关突变。这些结果表明，在日本人群中，除了线粒体DNA突变外，环境因素也参与了听力损失的发生，或者这些突变在该人群中不是致病性的。因此，国际数据库与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。本研究的数据可为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提供参考。

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.