药物性耳聋患者线粒体tRNA突变位点分析  

Mutational analysis of mitochondrial tRNA genes in patients with drug-induced deafness

作　　者：张静 胡光维 陆波 丁晓霞[2] ZHANG Jing;HU Guang-wei;LU Bo;DING Xiao-xia(Department of Otolaryngology,Zhoushan hospital,Zhoushan,Zhejiang,316000;Hangzhou First People＇s Hospital,Hangzhou,Zhejiang,310006)

机构地区：[1]舟山医院耳鼻喉科,浙江舟山316000 [2]杭州市第一人民医院,杭州310006

出　　处：《中国优生与遗传杂志》2018年第9期80-82,85,共4页Chinese Journal of Birth Health & Heredity

摘　　要：目的探讨线粒体tRNA基因突变与药物性耳聋的相关性,为耳聋的分子诊断提供理论依据。方法选取2016年1月到2017年10月在舟山医院就诊的被诊断为药物性耳聋的患者200人,同时选取100例性别与年龄相仿的正常人群作为对照组,采用PCR扩增22个线粒体tRNA基因组并进行测序分析,测序结果与线粒体的标准序列进行比对,确定突变位点。结果在这些患者中,我们共鉴定了5个药物性耳聋相关的tRNA突变位点:tRNAIle A4317G,tRNAAla T5655C,tRNASer(UCN)T7505C,tRNAArg T10454C,tRNAThr G15927A突变,而这些突变在正常人群中没有检测到。我们注意到这些突变大多位于进化上有着高度且保守的位点,其突变可能会引起线粒体tRNA的稳定性以及氨基酰化水平的下降,并因此会阻碍线粒体蛋白质的合成,线粒体的功能也会同时受到损伤,从而参与并影响了药物性的耳聋发病进程。结论线粒体tRNA基因是药物性耳聋相关的线粒体突变的热点区域,与耳聋相关的线粒体tRNA的突变筛查工作对于早期耳聋诊断和预防有着重要的意义。Objective：To explore the potential association between mitochondrial tRNA（mt-tRNA）mutations and deafness,and provided valuable information for molecular diagnosis of mitochondrial deafness. Methods：From January of 2016 to October of 2017,we recruited 200 patients with hearing loss and 100 gender-and age-matched healthy controls from Zhoushan Hospital. We used the PCR amplification of 22 mt-tRNA genes and subsequently sequenced the PCR products. The sequence data was then compared with the mitochondrial genome sequence and detected the mutations in mt-tRNA genes. Result：Of these patients,we identified 5 potential pathogenic mt-tRNA mutations,including tRNAIle A4317 G,tRNA^Ala T5655 C,tRNA^Ser（UCN）T7505 C,tRNA^Arg T10454 C,tRNA^Thr G15927 A,however,these mutations were absent in controls. We noticed that these mutations were localized at highly conserved nucleotides of the corresponding tRNAs,and may influence the steady-state level and the aminoacylation ability of tRNA and subsequently result the mitochondrial protein synthesis defects,and involved in the pathogenesis of deafness. Conclusion：Mutations in mt-tRNAs were the hot spots associated with hearing loss,screening for mttRNA mutations may be of clinical significance for early detection and prevention of mitochondrial deafness.

关 键 词：耳聋 线粒体突变 TRNA 功能损伤 

分 类 号：R764.4[医药卫生—耳鼻咽喉科]