细胞色素C氧化酶1基因T6253C点突变致线粒体脑肌病伴有高乳酸血症和卒中样发作综合征一例  

Cytochrome C oxidase subunit 1 mutation result in mitochondrial encephaiomyopathy with lactic acidosis and stroke-like episodes

作　　者：焦劲松[1] 张永庆[1] 杜皓萍[1] 王康[1] 汪仁斌[1] 王国相[1] 洪闻[2] 

机构地区：[1]中日友好医院神经内科,北京100029 [2]中日友好医院放射科,北京100029

出　　处：《中华神经科杂志》2007年第4期237-241,共5页Chinese Journal of Neurology

基　　金：卫生部部署医疗机构临床学科重点资助项目(2004-2006)

摘　　要：目的报道1例33岁男性,头痛后继以卒中样发作,影像学提示基底节区和颞枕叶缺血性改变,肌肉活检证实线粒体结构和功能异常的患者的基因突变。方法我们应用基因分析未发现常见致病性突变,因此应用 DNA 芯片扫描线粒体基因全序列,寻找可能的致病突变。通过 DNA 芯片扫描线粒体基因全序列,应用直接测序法证实突变。结果在线粒体 DNA 共发现了3个新突变,其中 T6253C 突变导致细胞色素 C 氧化酶1第117位保守的蛋氨酸被苏氨酸取代,患者的母亲也携带相同的突变,而98名健康个体无人携带此突变,我们认为 T6253C 是导致该患者发病的致病突变。结论这是首例关于细胞色素 C 氧化酶1基因点突变导致线粒体脑肌病伴有高乳酸血症和卒中样发作综合征的报道。Objective To report a 33-year-old man with post-headache stroke-like episodes, with whom ischemic changes were found in basal ganglia and occipital-temporal lobe and muscle biopsy revealed abnormal mitochondrial structure and function without regular mutations detected in mtDNA. Methods Gene chip technique was used to detect the mutation of whole sequence of mtDNA, and direct sequencing technique was used to confirm the mutations. Results Three mutations were found. A new mutation in the mitochondrial cytochrome C oxidase subunit 1 （MTCO1）, a T→C transition at nucleotide position 6253 resulted in conservative methionine transferring to threonine. His mother also held the mutation, which was not found in 98 control samples. So T6253C was considered the nosogenetic mutation. Conclusion This is the first time to report a mutation in MTCO1 responsible of MELAS.

关 键 词：线粒体脑肌病 酸中毒 乳酸性 脑血管意外 电子传递复合物Ⅳ 点突变 

分 类 号：R746[医药卫生—神经病学与精神病学]