母系遗传耳聋大家系的线粒体基因组全序列分析(英文)  

Sequence analysis of the mitochondrial genome from a large family with maternally inherited nonsyndromic deafness

作　　者：张海军[1] 徐春宏[1] 张艺飓 赵苏瑛[1] 单云峰[1] 耿雪侠[3] 单祥年[1] 

机构地区：[1]东南大学医学院遗传中心,南京210009 [2]江苏省疾病预防与控制中心 [3]淮北煤炭师范学院生物系

出　　处：《中华医学遗传学杂志》2005年第4期368-371,共4页Chinese Journal of Medical Genetics

基　　金：国家自然科学基金(30270731)~~

摘　　要：目的在江苏淮阴一母系遗传非综合征型耳聋大家系中,寻找线粒体基因组上可能影响1555(A→G)突变表型的其他位点突变。方法采用聚合酶链反应限制性片段长度多态性分析(PCRrestrictionfragmentlengthpolymorphism,PCRRFLP)和测序技术,检测了核心分支家系中27名母系成员的线粒体DNA上1555位点和7445位点的碱基变化,进而对该家系2名母系成员的线粒体全基因组和其他25名母系成员线粒体12SrRNA基因MTRNR1和tRNASer(UCN)基因MTTS1进行了全长测序。结果再次证明了1555(A→G)突变是该家系成员致聋的分子生物学基础之一;并发现该家系27名母系成员的线粒体基因组中除1555(A→G)突变外,还同时存在有955960(insC)同质型突变,两突变共分离。另外,新发现一个线粒体DNA突变———7449(insG),但该突变仅在2名母系成员中存在。结论推测955960(insC)突变可能通过改变12SrRNA基因的高级结构,并与1555(A→G)突变协同作用,提高了突变携带者对氨基糖甙类药物的敏感性;同时该突变可能也会导致线粒体蛋白质的合成缺陷,从而提高1555(A→G)突变致聋的外显率。Objective To ascertain whether other variations coexist with 1555（A→G） mutation in the mitoehondrial DNA and may aggravate the severity of hearing loss or increase the penetranee of 1555（A→G） mutation in alarge family with maternally inherited nonsyndromic deafness in Huaiyin, Jiangsu province. Methods PCR-restrietion fragment length polymorphism （PCR-RFLP） was used to screen both the nt1555 and the nt7445 of the mitoehondrial DNA from 27 maternal members in the core family; and then the mitnchondrial genomes from two maternal members, and the 12S rRNA genes MTRNR1 and tRNA-Ser^（UCN） gene MTTS1 from the others, were amplified by PCR-RFLP and were sequenced. Results 1555（A→G） mutation in the mitoehondrial DNA was revefified to be one of the major factors which cause maternally inherited nonsyndromic deafness and the cosegregation of 955-960（insC） and 1555 （A→G） was present in this family. Moreover,7449 （insG）, a novel homoplasmie mutation in the tRNA-Ser（UcN） gene, was found to co-exist with 1555（A→G） mutation in two maternal members. Conclusion The eosegregation of 955-960（insC） and 1555（A→G） implies that 955-960（insC） may synergistically cause hearing loss in the presence of an 1555（A→G） mutation, serving as an aggravating factor to enhance the sensitivity to aminoglyeosides, and may sometimes increase the penetranee of 1555（A→G） mutation.

关 键 词：母系遗传 耳聋 线粒体基因组 基因全序列 基因突变 

分 类 号：R764[医药卫生—耳鼻咽喉科]