浙江温岭167例非综合征型聋患者12S rRNA基因突变频谱分析  

Spectrum and frequency of mitochondrial 12S rRNA variants in 167 Chinese subjects with nonsyndromic hearing loss

作　　者：蔡朝阳[1] 应正标[1] 郑静[2] 张婷[3] 肖红利[4] 曾爱平[3] 周仁芳[3] 陈小友[1] 金士剑[1] 郑刚[1] 管敏鑫[2,4] 

机构地区：[1]温州医科大学附属温岭医院耳鼻咽喉科,浙江温岭317500 [2]浙江大学生命科学学院,浙江杭州310058 [3]温州医科大学附属温岭医院检验科,浙江温岭317500 [4]温州医科大学Attardi线粒体生物医学研究院,浙江温州325035

出　　处：《中国耳鼻咽喉头颈外科》2013年第10期525-529,共5页Chinese Archives of Otolaryngology-Head and Neck Surgery

基　　金：浙江省温岭市科技局科技资助项目(2011WLCA0052);中国博士后科学基金资助项目(2013M531472)联合资助

摘　　要：目的研究浙江温岭地区非综合征型聋患者的临床和分子遗传学特征。方法收集浙江温岭167例非综合征型聋患者,对线粒体12S rRNA基因进行突变筛查,从种系发生、结构-功能相关性及正常对照组的发生频率等方面评估12S rRNA基因变异与聋病的相关性。结果 12S rRNA基因上共鉴定23个变异,其中1555A>G、1027A>G和961位点变异分别占3.59%、0.60%和10.18%。872G>A突变位于12S rRNA基因的高度保守区域且未在449例正常对照组中发现,可能增加耳毒性药物的敏感性,其他变异位点为多态性位点。结论绘制温岭市非综合征型聋患者线粒体12S rRNA基因突变频谱,发现14.97%患者携带聋病相关12S rRNA基因突变。这些工作为聋病分子病因学研究、温岭地区聋病预防重点以及诊断方法的研发和聋病治疗提供重要数据。OBJECTIVE To investigate the clinical and genetic characteristics of subjects with non-syndromic hearing loss in Wenling City.METHODS A total of 167 Chinese hearing-impaired subjects were recruited from otology clinics of the First People＇s Hospital and Special Education School in Wenling City.These subjects underwent clinical,genetic evaluation and molecular analysis of mitochondrial 12S rRNA gene.Phylogenetic analysis,structural-functional correlation assessment and the occurrence rate of normal controls were performed to evaluate the correlation between 12S rRNA variants and hearing loss.RESULTS Mutational analysis identifed 23 variants（2 novel and 21 known）in the 12S rRNA gene in our cohort.The incidences of the known deafness-associated mutations at positions 1555,1027 and 961 were 3.59%,0.60% and 10.18% respectively.Other mtDNA variants were evaluated by structural and phylogenetic analysis.Of these,the 872G〉A variants conferred increased sensitivity to aminoglycosides or non-syndromic deafness as they were not present in 449 Chinese controls and localized at highly conserved nucleotides of this rRNA.However,other variants appeared to be polymorphisms.CONCLUSION The spectrum and frequency of variants in 12S rRNA gene was drawn among the subjects with non-syndromic hearing loss in Wenling City.As a result,mutations in mitochondrial 12S rRNA gene accounted for 14.97% cases of hearing loss patients in this cohort.Therefore,our findings may provide valuable information to further investigate the molecular etiology of deafness,to genetically prevent hearing loss in Wenling City and to develop the diagnostic methods and treatment of hearing loss.

关 键 词：听力障碍 氨基糖苷类 突变 线粒体 12S RRNA基因 

分 类 号：R764[医药卫生—耳鼻咽喉科]