线粒体DNAA8344G点突变的临床异质性表现  

Clinical heterogeneity associated with mitochondrial DNA A8344G point mutation

作　　者：赵娟[1] 赵丹华[1] 张巍[1] 吕鹤[1] 袁云[1] 戚豫 王朝霞[1] 

机构地区：[1]北京大学第一医院神经内科,100034 [2]中心实验室

出　　处：《中华医学杂志》2012年第40期2835-2838,共4页National Medical Journal of China

基　　金：国家自然科学基金（30870864）

摘　　要：目的报道线粒体DNA（mtDNA）A8344G点突变的临床特点。方法对北京大学第一医院1994--2011年10例经基因检查证实存在mtDNAA8344G点突变的患者，分析其临床表现和肌肉病理改变特点。结果6例患者表现为青少年起病的肌阵挛癫痫和小脑性共济失调，符合肌阵挛癫痫伴破碎红纤维（MERRF）综合征；2例患者为婴幼儿起病的以脑干和基底节病变为主的Leigh综合征；2例患者表现为成人起病的肢带型分布的线粒体肌病。10例患者均行骨骼肌病理检查，除1例MERRF患者外，其余患者均出现破碎红纤维（RRF）。肌肉组织中mtDNAA8344G突变比例定量分析显示，Leigh综合征患者（87．2％、88．4％）〉MERRF综合征（69．0％一86．8％）〉线粒体肌病患者（67．2％、58．4％）。结论mtDNAA8344G突变导致的临床类型存在明显的异质性，患者中肌肉mtDNA突变比例与临床表型可能有一定相关性，突变比例越高，临床严重程度越重。Objective To report the clinical features of mitochondrial disease caused by mitochondrial DNA （mtDNA） A8344G point mutation. Methods We analyzed the clinical presentations and muscular pathological changes in 10 patients with genetically confirmed mtDNA A8344G point mutation. Results Among them, 6 patients presented as juvenileonset myoclonic epilepsy with ragged red fibers （MERRF） syndrome, 2 suffered infantonset Leigh syndrome and the remaining 2 were diagnosed as limbgirdle mitochondrial myopathy. The mtDNA A8344G mutation load from muscle samples showed that patients with Leigh syndrome 〉 MERRF syndrome 〉 mitochondrial myopathy （ 87.2%, 88.4% 〉 69.0% - 86. 8% 〉 67.2%, 58.4% ）. Conclusions Mitochondrial disease caused by A8344G point mutation shows a great heterogeneity. The mutation load of muscle mtDNA might be associated with the severity of clinical phenotype, the higher mutation load, the more severe clinical presentations.

关 键 词：DNA 线粒体 点突变 MERRF综合征 LEIGH病 线粒体肌病 

分 类 号：R746[医药卫生—神经病学与精神病学]