A mutation in mitochondrial 12S rRNA, A827G, in Argentinean family with hearing loss after aminoglycoside treatment
A mutation in mitochondrial 12S rRNA, A827G, in Argentinean family with hearing loss after aminoglycoside treatment
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DOI：
10.1016/j.bbrc.2008.01.143
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发表时间：
2008-04-11
影响因子：
3.1
通讯作者：
Gerez, N. M.
中科院分区：
文献类型：
--
作者：
Chaig, M. R.;Zernotti, M. E.;Gerez, N. M.
线粒体DNA（mtDNA）突变与感音神经性听力损失有关。我们报告的临床，遗传和分子特征的一个阿根廷家庭与氨基糖苷类药物诱导的损害，在他们的两个成员。临床评估显示，这些受试者的听力障碍，包括听力配置的变量表型。对这些家系的mtDNA进行突变分析，发现存在与听力障碍相关的同质性12S rRNA A827 G突变。A827G突变位于哺乳动物中高度保守的线粒体12S rRNA基因的A位点。A827 G突变可能导致该rRNA的三级或四级结构改变，从而导致线粒体功能障碍，从而在听力损失和氨基糖苷类超敏反应的发病机制中发挥作用。然而，听力障碍的不完全突变表明A827G突变本身不足以产生临床表型。(c)2008年爱思唯尔公司All rights reserved.
Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report the clinical, genetic, and molecular characterization of one Argentinean family with aminoglycoside-induced impairment in two of their members. Clinical evaluation revealed the variable phenotype of hearing impairment including audiometric configuration in these subjects. Mutational analysis of the mtDNA in these pedigrees showed the presence of homoplasmic 12S rRNA A827G mutation, which has been associated with hearing impairment. The A827G mutation is located at the A-site of the mitochondrial 12S rRNA gene which is highly conserved in mammals. It is possible that the alteration of the tertiary or quaternary structure of this rRNA by the A827G mutation may lead to mitochondrial dysfunction, thereby playing a role in the pathogenesis of hearing loss and aminoglycoside hypersensitivity. However, incomplete penetrance of hearing impairment indicates that the A827G mutation itself is not sufficient to produce clinical phenotype. (c) 2008 Elsevier Inc. All rights reserved.