Leber遗传性视神经病变线粒体DNA原发性突变位点的分析

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。

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

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 11719G>A,would be a potential genetic bio-barcode of human mitochodrion.