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

目前还没有关于日本耳聋患者线粒体DNA整体上与耳聋相关的突变发生率的研究。为了阐明这个问题，我们着手分析了53名先天性耳聋患者、76名迟发性耳聋患者和144名听力正常的患者线粒体DNA中的耳聋基因。在对同源突变的分析中，在国际数据库中已报道与耳聋有关的突变在53例先天性耳聋患者中检测到8例，在76例迟发性耳聋患者中检测到4例。在异质性突变分析中，53例先天性耳聋患者中有7例检测到与耳聋相关的突变，76例迟发性耳聋患者中有7例检测到与耳聋相关的突变。在对正常听力对照组的分析中，144例受试者中有11例存在12S rRNA基因的耳聋相关突变，其余4个基因均无耳聋相关突变。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的。因此，国际数据库中与听力损失相关的线粒体遗传因素似乎与日本人群中的存在显著差异。为了进一步阐明日本人群中耳聋的遗传因素，以及在耳聋诊断中进行基因检测，应参考本研究报告的数据。

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.