中国华东地区家族性肌萎缩侧索硬化症患者SOD1基因突变检测及临床特点分析  

Screening of Mutations in SOD1 Gene and Aanalysis of Clinical Features of Patients with Familiar Amyotrophic Lateral Sclerosis in East China

作　　者：陈嬿[1] 董漪[1] 卢家红[1] 刘丰韬[1] 蒋雨平[1] 邬剑军[1] 

机构地区：[1]复旦大学附属华山医院神经内科,200040

出　　处：《中国临床神经科学》2016年第2期146-152,共7页Chinese Journal of Clinical Neurosciences

基　　金：上海市卫生计生委科研面上项目资助课题(编号:20124222)

摘　　要：目的对中国华东地区26例临床确诊为家族性肌萎缩侧索硬化症(FALS)家系的先证者进行铜锌超氧化物歧化酶(SOD1)的基因突变筛查。方法收集26例FALS家系先证者的外周血样本及临床资料。采用PCR技术结合DNA直接测序法对外周血DNA进行SOD1基因5个外显子的突变筛查,并分析SOD1基因突变与临床表型的关系。结果有6例先证者检测出3种SOD1突变。其中3例为位于2号外显子的已知错义突变p.His46Arg(c.140A>G),均表现为单侧下肢远端起病,上运动神经元损害不明显,平均病程可达10年以上。2例为位于2号外显子的已知错义突变p.Val47Ala(c.143T>C),临床表型较复杂,病变进展相对较快。1例为位于2号外显子新的错义突变p.Gly37Arg(c.112G>C),单侧上肢远端起病,上下运动神经元均受损,进展缓慢。结论中国华东地区FALS患者中SOD1基因突变仍占首位,突变与临床表型相关,其中His46Arg的临床表型具有特征性,有助于疾病预后判断。Aim To screen the Cu/Zn superoxide dismutase（SOD1） mutations in 26 probands who had been clinically diagnosed with familiar amyotrophic lateral sclerosis（FALS） in East China, and analyze the genotype-phenotype correlation of these patients. Methods Clinical data and blood samples of 26 FALS pedigrees were collected. SOD1 gene mutations in 26 probands were screened with PCR amplification and directly nucleotide sequenced. Then the correlations of genotype and phenotype were analyzed. Results There mutations were detected in exon 2 in 6 probands. Three probands carried the same p.His46Arg（c.140A〉G） mutations and 2 others carried p.Val47Ala（c.143T〉C） mutations. One novel mutation was p.Gly37Arg（c.112G〉C） detected in one young male proband. By reviewing all clinical data of these 6 pedigrees, p.His46 Arg led to a slow development and oneset from distal lowerlimb were found. Thedisease duration was more than 10 years. The phenotype of p.Val47 Ala is more complicated. This mutation displayed a relatively rapid progression and the part of disease onset was not the same even in one pedigree. The p.Gly37Arg（c.112G〉C） novel mutation displayed relatively slower progression. Conclusion SOD1 mutations are the mast common ones in FALS patients in East China. Mutations are related with clinical phenotypes. Among them, the phenotype of p.His46 Arg mutation is characteristic, which helps to predict the prognosis.

关 键 词：家族性肌萎缩侧索硬化 超氧化物歧化酶基因 突变 临床表型 

分 类 号：R744.8[医药卫生—神经病学与精神病学]