闽东南地区特教学校听力障碍学生线粒体基因变异调查  

Investigation of mitochondrial gene mutations in genetic or drug-induced hearing impaired students from special education school in southern Fujian

作　　者：吴阿阳[1,2] 杨惠聪[1,2] 伊强[3] 陈添彬[3] 刘奇才[3] 欧启水[3] 

机构地区：[1]福建省漳州市医院检验科,漳州363000 [2]福建医科大学附属漳州市医院,漳州361100 [3]福建医科大学附属第一医院检验科,福州350005

出　　处：《中华耳科学杂志》2012年第1期113-119,共7页Chinese Journal of Otology

基　　金：国家自然基金项目(81041108)

摘　　要：目的调查福建省闽东南地区特教学校遗传性或者药物性耳聋患者的分子遗传学病因。方法调查对象为福建省闽东和闽南3所特教学校276例听力障碍患者,对照组为按照疾病组进行年龄、性别匹配的健康体检者120例,所有的受试者均采集外周血并抽提DNA,应用基因芯片筛查国人常见的线粒体DNA(mtDNA)中的两个位点的突变,对可疑的母系遗传或药物性听力障碍患者应用限制性内切酶酶切结合直接测序技术对mtDNA进行全长分析,同时收集患者的相关临床资料。结果在37位可疑遗传性耳聋的先证患者中有7个存在明显的母系遗传特征,另外52人有氨基糖甙类药物接触史。共发现8例患者(2.91%)携带12SrRNA基因A1555G突变,12SrRNA基因C832T、T874C、G1125A和A1128G的变异位点;mtDNA存在着多种频率不等的变异形式,而且倾向于单体型的连锁出现,畲族患者以COⅠ和ATP6基因上的变异较为集中,包括C7196A、T7319C、G8997C、C8995T和C8994T等。结论线粒体DNA在非综合征耳聋患者中可以呈现多种形式的变异,其中12SrRNA基因A1555G突变在闽东南耳聋患者中具有一定的比例,而COⅠ和ATP6基因变异可能和种族遗传相关。Objective To survey molecular genetic factors in drug-induced or genetic deafness from southern among special education school students in southern Fujian. Method The survey was conducted in 276 patients with hearing disorder from three special education schools in southern Fujian. Age and sex matched healthy people （n=120） were selected as normal controls. DNA was extracted from peripheral blood. The common two mutations in mitochondrial DNA （mtDNA, 1555 A G and 1494 CT） were screened using the DNA microarray chips. When maternal inheritance or drug-induced hearing loss was suspected, whole length mtDNA was analyzed with restriction enzyme digestion and direct sequencing. Relevant clinical data were also collected in the patients. Results Thirty-seven probands were suspected of suffering from hereditary deafness. Additionally, 7 of them showed obvious maternal inheritance characteristics, while 52 patients had a history of exposure to aminoglycosides. Eight patients were found carrying the 12 S rRNA A1555G mutation. Furthermore, new 12S rRNA gene C832T, T874C, G1125A and A1128G mutation sites were also discovered in these patients. mtDNA mutations showed variation forms at variable frequencies with a tendency toward haplotypes. Mutations in patients of She ethnicity concentrated on the CO Ⅰ and ATP6 genes and included C7196A, T7319C, G8997C, C8995T, C8994T, etc. Conclsion Mitochondrial DNA in patients with non-syndromic deafness demonstrates many forms of variation, of which the 12 S rRNA gene 1555A G mutation shows a noticeable rate among patient population in southeastern Fujian. Variations on the COⅠand ATP6 genes seen in this study may be related with ethnicity.

关 键 词：听力障碍 线粒体DNA 变异 分子流行病学 

分 类 号：R394.34[医药卫生—医学遗传学]