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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.
Mutation of mitochondrial DNA is one of the important causes of hearing impairment, in which mitochondrial 12S rRNA gene mutation is associated with deafness syndrome and non-syndromic deafness, and most of the mitochondrial DNA mutations causing syndromic deafness are mostly heterogeneous, Non-syndromic deafness mutations are mostly homogeneity or heterogeneity, indicating that this molecular pathogenicity requires a higher threshold.A1555G and C1494T mutations in the 12S rRNA decoding region are caused by aminoglycoside antibiotics ear Toxic and non-syndromic deafness common molecular mechanism of these mutations may cause 12S rRNA secondary structure changes affect the synthesis of mitochondrial protein and reduce the production of intracellular ATP, the resulting mitochondrial dysfunction leading to deafness.However, most of the genes The pathogenic mechanism of the mutation is only in the speculation stage.Other modifying factors such as aminoglycoside antibiotics, mitochondrial haploids and nuclear modification genes are involved in deafness phenotypes associated with mitochondrial 12SrRNA A1555G and C1494T mutations.