编码酶复合体I亚单位的线粒体基因新突变导致的MELAS综合征  

Novel mutations in the mitochondrial DNA encoded complex I subunit genes associated with MELAS

作　　者：赵丹华[1] 王朝霞[1] 李务荣[1] 洪道俊[1] 郑日亮[1] 孙永安[1] 张巍[1] 袁云[1] 

机构地区：[1]北京大学第一医院神经内科,北京100034

出　　处：《中风与神经疾病杂志》2011年第9期772-775,共4页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金资助(No.30870864)

摘　　要：目的报道4例由编码酶复合体I中NADH脱氢酶(ND)亚单位的线粒体基因(mtDNA)突变所导致的线粒体脑肌病患者,分析其临床及骨骼肌病理改变特点。方法 4例患者的发病年龄在6～21岁之间,病程在7～20年。其中1例为MELAS、3例为MELAS/Leigh叠加综合征。对4例患者进行肌肉活检和mtDNA全长测序检查。结果骨骼肌病理检查发现1例同时存在破碎红纤维(RRFs)及SDH深染的血管(SSVs),2例仅有SSVs,另1例未见异常。4例患者均携带mtDNA编码的ND基因突变,分别为位于ND3编码区的T10191C(p.S45P)、ND4编码区的A11470C(p.K237N)、ND5编码区的T13046C(p.M237T)点突变以及累及ND5和ND6编码区的单一大片段缺失(13025-13033:14417-14425),后3种突变均为新发现的致病性突变。结论 ND基因突变是导致部分MELAS或MELAS/Leigh叠加综合征患者的分子病理学基础,这些患者的骨骼肌病理检查常缺乏典型的线粒体脑肌病的病理改变,如RRFs。Objective To report the clinical and myopathological features of 4 patients with mitochondrial encephalomyopathy associated with mutations in mitochondrial DNA(mtDNA) encoded NADH dehydrogenase(ND) subunit genes of complex I.Methods The onset age of 4 patients ranged from 6 to 21 years,with a clinical course from 7 to 20 years.Among them,1 case was consistent with MELAS and 3 cases with MELAS/Leigh overlap syndrome.Muscle biopsy and whole sequencing of mtDNA were performed on these patients.Results Skeletal muscle biopsy disclosed both ragged-red fibers(RRFs) and strongly succinate dehydrogenase-reactive vessels(SSVs) in one case,only SSVs without RRFs in two cases,and no abnormality in one.Whole sequencing of mtDNA revealed T10191C(p.S45P) in ND3,A11470C(p.K237N) in ND4,T13046C(p.M237T) in ND5 and a single large-scale deletion ranging from 13025-13033 to 14417-14425 encompassing ND5 and ND6 in these patients respectively.Among them,A11470C,T13046C and the deletion were novel mutations.Conclusion Mutations in ND genes are important molecular pathologic basis of MELAS or MELAS/Leigh overlap syndrome.Typical myopathlogical features of mitochondrial encephalomyopathy,such as RRFs,could be absent in these patients.

关 键 词：酶复合体I ND基因 线粒体DNA 突变 MELAS综合征 MELAS/Leigh叠加综合征 

分 类 号：R746[医药卫生—神经病学与精神病学]