氨基甙类抗牛素耳毒性与线粒体基因突变分析

Aminoglycoside ototoxicity associated with mitochondrial DNA mutation

进一步证明遗传因素对氨基甙类抗生素耳毒性的作用，探讨该病的发病机理。方法：应用ＰＣＲ-限制性酶切方法分析了９个氨基甙类抗生素致聋家系中６２个成员线粒体ＤＮＡ。结果：发现５个家系中２０例线粒体ＤＮＡ１２５ｒＲＮＡ基因第１５５５位Ａ→Ｇ点突变。结论：该突变是氨基甙类抗生素耳毒性遗传易感性的分子生物学基础。可能有其他线粒体ＤＮＡ基因突变与氨基甙类抗生素耳毒性有关。

Objective:To confirm the effect of genetic susceptibility to aminoglycoside ototoxicity. Method:Mitochondrial DNA(mtDNA) from 62 members of 9 aminoglycoside induced deafness families was analysed byPCR-Restriction endonuclease digestion. Result:The nucleotide 1555A G mutation in 12S rRNA gene of mtD-NA was identified in 20 members of 5 families. Conclusion:These findings indicate that this mutation is a molecular basis for genetic susceptibility to the ototoxic effect of aminoglycosides. The relationship between the au-diovestibular changes and genetic susceptibility to aminoglycoside ototoxicity and the pathogenetic mechanism ofsusceptible deafness are discussed. The possibility that other gene mutations can also predispose to aminoglycoside ototoxicity is proposed.