Leber遗传性视神经病变线粒体DNA原发性突变位点的分析  

Analysis of primary mitochondrial DNA mutations of Chinese patients with leber's hereditary optical neuropathy (LHON)

作　　者：杜卫东[1,2,3] 吕永梅[1] 汤华阳[1] 黄叔仁 陈大本[5] 何祥成 王永清 孙松[5] 张学军[1,2,3] 徐昌娟（校） 

机构地区：[1]安徽医科大学皮肤病研究所,安徽合肥230032 [2]安徽医科大学第一附属医院皮肤科,安徽合肥230022 [3]省部共建教育部重要遗传病基因资源利用重点实验室,安徽省基因研究重点实验室,安徽合肥230032 [4]安徽省红十字会眼科医院,安徽合肥230022 [5]中国科技大学医院眼科,安徽合肥230026 [6]不详

出　　处：《疾病控制杂志》2006年第6期574-579,共6页Chinese Journal of Disease Control and Prevention

基　　金：国家自然科学基金(30470591);安徽省"十五"高校学科拔尖人才基金

摘　　要：目的探讨Leber遗传性视神经病变(LHON)线粒体DNA原发性突变特征。方法利用Pyrosequencing和测序技术对11个LHON家系的13例典型患者及其30位家系成员11778G>A等12余种线粒体DNA突变位点进行分析。结果本地区LHON患者均为线粒体DNA同质性突变(homoplasmy)。11个LHON家系中有7个分别含有11778G>A,14484T>C和3460G>A原发性突变位点,占63.6%(7/11例)。13例患者线粒体DNA突变以11778G>A为主(53.8%,7/13例)。13708G>A和3552T>A突变单独存在于2个LHON家系中。3460G>A与3394T>C合并存在。未发病家系成员中可见11778G>A,14484T>C,13708G>A纯合性或杂合性突变体。结论继发性突变位点可单独存在,也可与原发性突变位点合共同导致LHON的发病。11719 G>A可能成为人线粒体有用的生物标签。Objective To question the characteristics of primary mitochondrial DNA mutations in Chinese patients with Leber＇s hereditary optical neuropathy （LHON）. Methods Twelve mutations in 13 patients and 30 members from 11 LHON pedigrees were investigated with Pyrosequencing and DNA sequencing techniques. Results All the mitochondrial DNA mutations of the LHON patients in this study are homoplasmy. Seven of the 11 pedigrees showed 11778G〉A, 14484T 〉C and 3460G〉 A, respectively, accounting for 63.6 % （7/11 ）. 11778G 〉 A mutation in these patients is prevalent （53.8 %, 7/13）. 13708G）〉 A and 3552T〉 A mutations occurred alone in two LHON pedigrees, respectively. 3460G〉 A and 3394T 〉 C mutations were found to co-exist in LHON. Either homoplasmy or heteroplasmy 11778G 〉 A, 14484T 〉 C and 13708G 〉 A appeared in LHON pedigree members who showed no clinical manifestation. Conclusions Secondary mutations not only alone but integrating with primary mutations led to LHON pathogenesis. The l1719G〉A, would be a potential genetic bio-bareode of human mitochodrion.

关 键 词：视神经疾病 DNA 线粒体 点突变 DNA突变分析 

分 类 号：R774.6[医药卫生—眼科]