与耳聋相关的线粒体12S rRNA突变

线粒体DNA突变是引起听力损伤的重要原因之一. 其中，线粒体12S rRNA基因突变与综合征型耳聋和非综合征型耳聋相关. 导致综合征型耳聋的线粒体DNA突变多为异质性，然 而对于非综合征型耳聋突变则多以同质性或高度异质性存在，说明这种分子致病性需要较高的阈值. 位于12S rRNA解码区的A1555G和C1494T突变是造成氨基糖甙类抗生素耳毒性和 非综合征型耳聋常见的分子机制. 这些突变可能造成12S rRNA二级结构的改变，影响线粒体蛋白质的合成，降低细胞内ATP的产生，由此引起的线粒体功能障碍导致耳聋. 但是多数 基因突变的致病机制还仅处于推测阶段. 其它修饰因子如氨基糖甙类抗生素、线粒体单体型、核修饰基因参与了线粒体12S rRNA基因A1555G和C1494T突变相关的耳聋表型表达.

Mitochondrial 12S rRNA Mutations Associated with Deafness

Mutations in mitochondrial DNA(mtDNA) are one of the important causes of hearing loss.In particular,mutations in the mitochondrial 12S rRNA gene is associated with syndromic or non-syndromic hearing loss.Syndromic deafness-associated mtDNA mutations occurred with heteroplasmy,while the non-syndromic mtDNA mutations showed either homoplasmy or high levels of heteroplasmy,indicating a high threshold for molecular pathogenicity of non-syndromic hearing loss.The A1555G and C1494T mutations at highly conserved regions of 12S rRNA gene linked to a significant number of cases of aminoglycoside ototoxicity and non-syndromic deafness.The mutations may alter the secondary structures of mitochondrial 12S rRNA,impair mitochondrial translation and decrease the ATP production.Consequently,mitochondrial dysfunctions caused by these mutations eventually lead to hearing loss.The pathogenic mechanism of these gene mutations proposed by far remained to be tested experimentally.The other factors,including aminoglycosides,mitochondrial haplotypes or nuclear modifier genes might also contribute to the phenotypic manifestation of the A1555G and C1494T mutations.