中国人群携带m.14484T>C突变的Leber’s遗传性视神经病变线粒体单体型及多态位点分析  

The analysis of mitochondrial DNA haplogroups and variants for Leber's hereditary optic neuropathy in Chinese families carrying the m.14484T>C mutation

作　　者：孟祥娟[1,2] 朱金萍[1,2] 高敏[1,2] 张赛[1,2] 赵福新[2] 张娟娟[3] 刘晓玲[2] 韦企平[4] 童绎[2] 张铭连[5] 瞿佳[2] 管敏鑫[1,3] 

机构地区：[1]温州医科大学Attardi线粒体生物医学研究院,浙江省医学遗传学重点实验室,温州325035 [2]温州医科大学附属眼视光学院,温州325027 [3]浙江大学遗传研究所,杭州310023 [4]北京中医药大学东方医院,北京100078 [5]河北省邢台市眼科医院,邢台054001

出　　处：《遗传》2014年第4期336-345,共10页Hereditas（Beijing)

基　　金：国家自然科学基金项目(编号:81200724);国家科技支撑计划(编号:2012BAI09B03);温州医科大学附属眼视光医院创新引导课题(编号:YNCX201010)资助

摘　　要：线粒体ND6基因（MT-ND6）上的m.14484T＞C突变是Leb er＇s遗传性视神经病变（Leber＇s hereditary optic neuropathy,LHON）的一个原发性突变,但该突变自身不足以产生视力损伤.为研究线粒体单体型对携带该突变人群LHON发病的影响,文章对1 177例中国汉族LHON患者MT-ND6基因进行了全面系统的筛查,共筛查到67例患者携带m.14484T＞C同质性突变,在该研究群体中所占比例为5.7％.携带m.14484T＞C突变的51例家系LHON的外显率从5.6％～100.0％不等,平均外显率为21.5％.对家系中51例先证者线粒体全基因组进行分析,各表现为不同的多态性,分别属于18个东亚线粒体单体型.其中单体型A和单体型F在病例组频率均明显低于106例对照组.另外,单体型M10a在病例组中占9.8％,在对照组中未被发现,进一步发现该单体型家系LHON的平均外显率（46.13％）显著高于其他单体型家系的平均外显率,提示线粒体单体型M10a可能增加视力损伤的风险.The m.14484T＞C mutation in mitochondrial ND6 gene （MT-ND6） is a primary mutation underlying the development of Leber＇s hereditary optic neuropathy （LHON）,but by itself not enough to cause visual loss.To explore the role of mitochondrial haplogroups on the expression of LHON for the people carrying the m.14484T＞C mutation,we performed systematic and extended mutational screening of MT-ND6 gene in a cohort of 1177 Han Chinese patients with LHON.A total of 67 affected subjects carried the homoplasmic m.14484T＞C mutation,accounting for 5.7％ of this LHON population.The penetrances of optic neuropathy among 51 pedigrees carrying the m.14484T＞C mutation ranged from 5.6％ to 100.0％,with the average of 21.5％.The sequence analysis of entire mitochondrial genomes of 51 probands exhibited distinct sets of polymorphisms belonging to 18 Eastern Asian haplogroups.The frequencies of haplogroup A and haplogroup F were significantly less in the LHON mtDNA samples than those in 106 Chinese controls.On the other hand,the haplogroup M10a accounted for 9.8％ of the patient＇s mtDNA samples but was absent in 106 Chinese controls.Strikingly,the average penetrance （46.13％） of optic neuropathy for the pedigrees carrying mitochondrial haplogroup M10a was higher than those carrying other mtDNA haplogroups.These observations indicated that mitochondrial haplogroup M10a may increase the risk of visual loss.

关 键 词：LEBER遗传性视神经病变 线粒体 突变 单体型 外显率 

分 类 号：R394[医药卫生—医学遗传学]