线粒体脑肌病伴高乳酸血症和卒中样发作综合征的分子生物学特征  

Molecular biological characteristics of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes

作　　者：吴世陶[1] 刘方[1] 石伟伟 张敏[1] 李建章[2] 刘恒方[1] WU Shitao;LIU Fang;SHI Weiwei;ZHAGN Min;LI Jianzhang;LIU Hengfang(The Fifth Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China;The Second Affiliated Hospital of Zhengzhou University,Zhengzhou 450003,China)

机构地区：[1]郑州大学第五附属医院,河南郑州450052 [2]郑州大学第二附属医院,河南郑州450003

出　　处：《中国实用神经疾病杂志》2021年第13期1124-1131,共8页Chinese Journal of Practical Nervous Diseases

基　　金：河南省卫健委省部联合科技攻关项目(编号:SB201901056)。

摘　　要：目的探讨线粒体脑肌病伴高乳酸血症和卒中样发作综合征的分子生物学特征。方法收集2011-01—2020-01郑州大学第五附属医院和郑州大学第一附属医院经肌肉病理和基因测序同时确诊的42例MELAS综合征的临床表现、影像学、肌肉病理和基因测序等资料,对其血液和新鲜尿液的基因测序结果进行回顾性分析。结果42例患者均发现mtNDA突变,30例患者发生3243 A>G突变,血液检出25例发生3243 A>G突变,突变率为22.15%~100%(36.26±13.38)%;尿液检出30例发生3243 A>G突变,细胞突变率为38.46%~100%(59.49±22.67)%;发现3271 T>C突变、13513 G>A突变分别3例,1642 G>A、3093 C>G、3256 C>T、3302 A>G、3697 G>A和15242 G>A突变分别1例,其中3093 C>G、3697 G>A和15242 G>A突变国外已经报道,而国内尚未见报道。与血液的线粒体DNA突变率相比,尿液的突变率显著增高,差异有统计学意义(P<0.05)。结论3243 A>G是MELAS综合征最常见的突变位点。3093 C>G、3697 G>A和15242 G>A突变丰富了国内MELAS综合征线粒体基因突变的特点。尿液的mtDNA突变率高于血液,可作为MELAS综合征患者及亲属基因测序的首选标本。Objective To investigate the molecular biological characteristics of imaging in mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes(MELAS)syndrome.Methods The clinical manifestations,imaging,muscle pathology and gene sequencing of 42 cases of MELAS syndrome confirmed by muscle pathology and gene sequencing in the Fifth Affiliated Hos⁃pital of Zhengzhou University and the First Affiliated Hospital of Zhengzhou University from January 2011 to January 2020 were col⁃lected,and the results of gene sequencing of their blood and fresh urine were analyzed retrospectively.Results Mt DNA mutations were found in all 42 patients.30 patients had 3243 A>G mutation,25 patients of peripheral blood had 3243 A>G mutation,and the mutation rate was 22.15%-100%,with an average of(36.26±13.38)%.30 cases of urine cells occurred 3243 A>G mutation,and the mutation rate was 38.46%-100%,with an average of(59.49±22.67)%.3271 T>C mutation and 13513 G>A mutation were found re⁃spectively in three cases,and the 1642 G>A,3093 C>G,3256 C>T,3302 A>G,3697 G>A and 15242 G>A mutations were found respectively in one case.Among them,3093 C>G,3697 G>A and 15242 G>A had been reported abroad,but there was no re⁃port in our country.No mutations were found in the fathers of all patients.Compared with the rate of mitochondrial DNA mutation in peripheral blood,the mutation rate of urine cells was significantly higher,and the difference was statistically significant(P<0.05).Conclusion The 3243 A>G was the most common mutation site.The three mutations of 3093 C>G,3697 G>A and 15242 G>A in this group were reported for the first time in China,which enriched the characteristics of mitochondrial gene mutation in MELAS syn⁃drome in our country.The rate of mtDNA mutation in urine cells was higher than that in peripheral blood.Urine cells could be used as the first choice for gene sequencing in patients with MELAS syndrome and relatives.

关 键 词：线粒体脑肌病伴高乳酸血症和卒中样发作综合征 肌肉病理 血液 尿液 基因突变 特征 

分 类 号：R746[医药卫生—神经病学与精神病学]