Leigh综合征患儿核基因和线粒体基因突变的初步分析  

Mutation analysis on nuclear gene and mitochondrial gene for Chinese patients with Leigh syndrome

作　　者：张尧[1] 孙芳[1] 孔庆鹏[2] 魏晓琼[1] 戚豫[3] 张英[3] 马祎楠[3] Sayami Sujan 王朝霞[4] 袁云[4] 杨艳玲[1] 姜玉武[1] 秦炯[1] 

机构地区：[1]北京大学第一医院儿科,北京100034 [2]中国科学院昆明动物所细胞与分子进化实验室,云南昆明650000 [3]北京大学第一医院中心实验室,北京100034 [4]北京大学第一医院神经内科,北京100034

出　　处：《临床儿科杂志》2008年第12期1021-1025,共5页Journal of Clinical Pediatrics

基　　金：国家自然科学基金面上项目(No.30471832);十一五国家科技支撑计划项目(No.2006BAI05A07)

摘　　要：目的探讨中国人Leigh综合征患儿的发病机制,并对已知的部分核基因和线粒体基因突变进行分析。方法对1992-2006年收集的来自我国28个省、自治区或直辖市的145例Leigh综合征患儿进行病因学分析。在排除SURF1基因和线粒体基因T8993G、T8993C、A8344G、A3243G四个位点突变后,对80例患儿的丙酮酸脱氢酶E1α亚单位基因(PDHA1)进行PCR扩增和测序分析;并在此基础上对9个线粒体DNA突变位点(G13513A、A13084T、T10158C、C11777A、T10191C、T14487C、T12706C、9537insC和T9176G)进行突变筛查。另对23例A3243G线粒体DNA突变阳性的患儿进行SURF1基因的分析。结果80例患儿中仅1例携带PDHA1基因突变,为214位点C>T转换,导致PDHA1蛋白第27位氨基酸由精氨酸变为半胱氨酸。而64例患儿其他9个线粒体DNA突变位点筛查均为阴性。在23例携带线粒体DNAA3243G突变的患儿中,6例携带SURF1基因G604C杂合性变异。结论由于Leigh综合征病因复杂多样,使突变分析难于获得阳性结果。为缩小突变筛查的范围,明确Leigh综合征患儿的病因,亟待建立适用于临床检测应用的线粒体呼吸链酶学的测定方法。Objectives To explore the etiology of Leigh syndrome for Chinese population, and to perform mutation analysis on pyruvate dehydrogenase E1 α-subunit （PDHA1） gene and mitochondrial DNA （mtDNA）. Methods One hundred fourty-five patients with Leigh syndrome from 28 provinces or cities from China's Mainland were studied from 1996 to 2006. PDHA1 gene was amplified with PCR technique and sequenced in 80 patients, after excluding the mutations on SURF1 gene and four point mutations （including T8993G, T8993C, A8344G and A3243G） on mtDNA. Nine point mutations （G13513A, A13084T, T10158C, C11777A, T10191C, T14487C, T12706C, 9537insC and T9176G） on mt- DNA were analyzed in 64 patients without T8993G, T8993C, A8344 G and A3243G mutations. Mutation analysis for SURF1 gene was done on 23 patients with A3243G mutation on mtDNA. Results C214T mutation on PDHA1 gene was detected in a boy. Nine point mutations on mitochondrial genome were negative in 64 patients. Six of the 23 patients with A3243G mutation on mtDNA were identified as having a heterogeneous G604C variation on SURF1 gene. Conclusions The complicated genetic defects of Leigh syndrome makes it hard to perform genetic studies. Therefore, it is essential to establish an enzyme assay for mitochondrial respiratory chain in order to minimize the screening scope and clarify the etiology of Leigh syndrome.

关 键 词：LEIGH综合征 丙酮酸脱氢酶E1α亚单位 线粒体DNA 突变 

分 类 号：R748[医药卫生—神经病学与精神病学]