MT-ND1 m．3635G＞A突变在Leber遗传性视神经病变发病中的作用  

The role of MT-ND1 m. 3635G 〉 A mutation in Leber＇ s hereditary optic neuropathy

作　　者：张娟娟[1,2] 张增君 付汝宁 冀延春[3] 蒋萍萍[3] 童绎 瞿佳[1] 管敏鑫[2,3] 

机构地区：[1]温州医科大学眼视光学院、附属眼视光医院,浙江325027 [2]Attardi线粒体生物医学研究院 [3]浙江大学医学院遗传学研究所,杭州310023 [4]福州东南眼科医院,350002

出　　处：《中华医学遗传学杂志》2016年第6期747-751,共5页Chinese Journal of Medical Genetics

基　　金：“十二五”国家支撑计划项目（2012BA109803）;国家自然科学基金（31471191,81200724,81400434）;浙江省钱江人才项目（2013R10042）

摘　　要：目的阐明MT-ND1 m．3635G＞A导致Leber遗传性视神经病变（Leber＇s hereditary optic neuropathy, LHON）的发病机制。方法比较对照组和携带者组之间以及对照组和病例组之间永生淋巴细胞系的呼吸链复合体酶活力、三磷酸腺苷（adenosine-triphosphate，ATP）合成和氧消耗速率。结果通过对携带者组、病例组与对照组永生淋巴细胞系的线粒体功能进行研究，发现病例组复合体I酶活力比对照组下降51．0％（P＜0．05）；病例组细胞内总ATP合成为对照组的35．8％～73．2％，平均为50．7％（P〈0．05）；细胞的氧消耗速率（oxygen consumptionrate，OCR）测定表明病例组基础OCR（P＜0．05）、ATP偶联OCR（P＜0．05）和最大OCR（P＜0．05）与对照组相比均有不同程度的降低。结论 m．3635G＞A导致线粒体功能障碍，是LHON相关的致病性突变。Objective To investigate the role ofMT-ND1 m. 3635G〉A mutation in the pathogenesis of Leber＇s hereditary optic neuropathy （LHON）. Methods Biochemical characteristics including the activity of complex Ⅰ , ATP production and oxygen consumption rate among lymphoblastoid cell lines derived from 3 carriers, 3 affected matrilineal relatives of the families and 3 controls were compared. Results Comparison of mitochondrial functions in lymphoblastoid cell lines of the carriers, patients and controls showed a 51.0% decrease in the activity of complex Ⅰ in patients compared with controls （P〈0. 05）. The m. 3635G〉A mutation has resulted in decreased efficiency of ATP synthesis （P〈0.05）. Comparison of oxygen consumption rate showed that the basal OCR （P〈0. 05）, ATP-linked OCR （P〈0.05） and the maximum OCR （P 〈 0.05） have all reduced to some extent compared with the controls. Conclusion These results showed that m. 3635G〉A, as a LHON-associated mutation, can lead to rnitochondrial dysfunction.

关 键 词：LEBER遗传性视神经病变 中国人群 线粒体ND1基因 突变 功能障碍 

分 类 号：R77[医药卫生—眼科]