与耳聋相关的线粒体12S rRNA突变  

Mitochondrial 12S rRNA Mutations Associated with Deafness

作　　者：张婷[1,2] 曾爱平[2] 郑静[1] 管敏鑫[1,3] 

机构地区：[1]温州医学院Attardi线粒体生物医学研究院和浙江省医学遗传学重点实验室,浙江温州325035 [2]温岭市第一人民医院检验科暨温州医学院附属温岭医院检验科,浙江温岭317500 [3]浙江大学生命科学学院遗传学研究所,浙江杭州310058

出　　处：《中国生物化学与分子生物学报》2012年第4期316-325,共10页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.81070794);国家"973"重大基础研究前期研究专项(No.2004CCA02200);浙江省重大科技专项社会发展项目(No.2007C13021)~~

摘　　要：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12SrRNA基因A1555G和C1494T突变相关的耳聋表型表达.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.

关 键 词：线粒体12S RRNA 突变 耳聋 修饰因子 

分 类 号：Q75[生物学—分子生物学] R394[医药卫生—医学遗传学]