Department of Biotechnology, Nanjing Medical University, Nanjing, China.
Int J Audiol. 2013 Feb;52(2):98-103. doi: 10.3109/14992027.2012.743046. Epub 2012 Dec 13.
To explore the molecular genetic characterization of two Chinese families with aminoglycoside-induced and non-syndromic hearing loss (NSHL).
Clinical evaluations, sequence analysis of mitochondrial DNA (mtDNA) as well as two nuclear genes TRMU and MTO1 encoding mitochondrial proteins.
Two Chinese families with aminoglycoside-induced and NSHL.
Clinical evaluations revealed incomplete penetrance (28.6% vs. 40.0%) and variable phenotype of hearing losses between two families. When the effect of aminoglycosides was excluded, the penetrances were both 0%. Sequence analysis of mitochondrial genomes showed a homoplasmic 1494C > T mutation in the12S rRNA gene (MT-RNR1) in all maternal relatives, as well as distinct sets of mtDNA polymorphism belonging to Eastern Asian haplogroups D4j and D5a2, respectively. However, none of these mtDNA variants was highly evolutionarily conserved and implicated to have functional significance. No mutations were identified in either TRMU or MTO1 gene.
Mitochondrial 1494C> T mutation is the molecular basis responsible for the NSHL of two families, and the use of aminoglycoside antibiotics can worsen the hearing of the mutation carriers. Our results indicate the importance of a systematic screening for the mitochondrial 1494C > T mutation in Chinese subjects in the prevention of aminoglycoside-induced and non-syndromic hearing loss.
探讨两个中国氨基糖苷类药物诱导性及非综合征型听力损失（NSHL）家系的分子遗传学特征。
临床评估、线粒体 DNA（mtDNA）序列分析以及编码线粒体蛋白的两个核基因 TRMU 和 MTO1。
两个中国氨基糖苷类药物诱导性及非综合征型听力损失家系。
临床评估显示两个家系听力损失存在不完全外显率（28.6% vs. 40.0%）和表型变异性。当排除氨基糖苷类药物的影响时，外显率均为 0%。线粒体基因组序列分析显示，12S rRNA 基因（MT-RNR1）中的同质突变 1494C > T 存在于所有母系亲属中，以及分别属于东亚单倍群 D4j 和 D5a2 的独特 mtDNA 多态性。然而，这些 mtDNA 变体都没有高度进化保守性，也没有功能性意义。在 TRMU 或 MTO1 基因中均未发现突变。
线粒体 1494C > T 突变是两个家系 NSHL 的分子基础，氨基糖苷类抗生素的使用会使突变携带者的听力恶化。我们的结果表明，在中国人群中进行系统性的线粒体 1494C > T 突变筛查对于预防氨基糖苷类药物诱导性及非综合征型听力损失非常重要。
