Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss
Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss
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DOI：
10.1007/s00439-005-1276-1
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发表时间：
2005-06-01
期刊：
影响因子：
5.3
通讯作者：
Guan, MX
中科院分区：
文献类型：
--
作者：
Li, ZY;Li, RH;Guan, MX
线粒体DNA（mtDNA）突变与感音神经性听力损失有关。我们在这里报告了一个系统的线粒体12S rRNA基因突变筛查128例中国儿童受试者散发性氨基糖苷类药物诱导的非综合征性听力损失。我们发现，氨基糖苷类耳毒性占中国儿童听力损失病例的48%。在该基因的已知遗传相关突变中，A1555G突变的发生率在中国儿童氨基糖苷类诱导性听力损失人群和非综合征性听力损失人群中分别为13%和2.9%。此外，在中国临床人群中，12S rRNA基因第961位突变分别占氨基糖苷类诱导性和非综合征性听力损失病例的1.7%和4.4%。T1095C突变已被确定在一个母系遗传的家庭与氨基糖苷类药物诱导的非综合征性听力损失。然而，在该临床人群中未检测到C1494T突变。此外，12S rRNA基因中位于高度保守位点的三个变体A827 G、T1005 C和A1116 G可能在氨基糖苷类耳毒性的发病机制中发挥作用。这些数据有力地表明，线粒体12S rRNA是中国人群中与生育相关的突变的热点。
Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report here a systematic mutational screening of the mitochondrial 12S rRNA gene in 128 Chinese pediatric subjects with sporadic aminoglycoside-induced and non-syndromic hearing loss. We show that aminoglycoside ototoxicity accounts for 48% of cases of hearing loss in this Chinese pediatric population. Of the known deafness-associated mutations in this gene, the incidence of the A1555G mutation is similar to 13% and similar to 2.9% in this Chinese pediatric population with aminoglycoside- induced and non-syndromic hearing loss, respectively. Furthermore, mutations at position 961 in the 12S rRNA gene account for similar to 1.7% and 4.4% of cases of aminoglycoside-induced and non-syndromic hearing loss in this Chinese clinical population, respectively. The T1095C mutation has been identified in one maternally inherited family with aminoglycoside-induced and non-syndromic hearing loss. However, the C1494T mutation was not detected in this clinical population. In addition, three variants, A827G, T1005C and A1116G, in the 12S rRNA gene, localized at highly conserved sites, may play a role in the pathogenesis of aminoglycoside ototoxicity. These data strongly suggest that the mitochondrial 12S rRNA is a hot-spot for deafness-associated mutations in the Chinese population.