肌萎缩侧索硬化患者SOD1基因突变检测及突变与临床表型的关系  

Screening of mutations in SOD1 gene and analysis of genotype-phenotype correlation in Chinese patients with amyotrophic lateral sclerosis

作　　者：牛艳芳[1,2] 熊慧玲[1,2] 邬剑军[2] 陈嬿[2] 乔凯[2] 吴志英[1,2] 

机构地区：[1]福建医科大学附属第一医院神经内科,福州350005 [2]复旦大学附属华山医院神经内科,上海200040

出　　处：《遗传》2011年第7期720-724,共5页Hereditas（Beijing)

基　　金：福建省高校创新团队培育计划项目(编号:FMU-RT002)资助

摘　　要：应用PCR技术结合DNA直接测序方法对8例临床确诊为家族性肌萎缩侧索硬化(Familiar amyotrophic lateral sclerosis,FALS)家系的先证者进行铜锌超氧化物歧化酶基因(SOD1)的突变筛查,在3例先证者中检出2种SOD1基因突变,其中,2例携带了位于4号外显子的错义突变Cys111Tyr(c.332G>A),另1例携带了位于5号外显子的错义突变Gly147Asp(c.440G>A),这2种突变在中国ALS患者中属首次报道。该结果扩大了中国FALS患者的SOD1基因突变谱,对研究中国FALS患者SOD1基因突变特点和分布规律有一定帮助。分析携带这2个突变患者的临床特点,提示Cys111Tyr突变导致的临床表型相对温和,而Gly147Asp突变可导致病情进展较快。该结果有待在更多的病例中进行证实。In this study,we screened for the Cu/Zn superoxide dismutase（SOD1） mutations in 8 probands who had been clinically diagnosed with familiar amyotrophic lateral sclerosis（FALS） using PCR and direct sequencing.Two known mu-tations were detected in the three probands.Two probands carried the same Cys111Tyr（c.332GA） mutation in exon 4,and others carried Gly147Asp（c.440GA） mutation in exon 5.These two mutations were first reported in the Chinese ALS patients.After reviewing all clinical data of these three pedigrees,we found that Cys111Tyr led to a relatively mild pheno-type and Gly147Asp displayed a rapidly progression,which needs to be confirmed by further study in more ALS patients.In conclusion,this study extends the spectrum of SOD1 mutations in the Chinese FALS patients and facilitates to investi-gate characteristics and distribution of SOD1 mutations in the Chinese population.

关 键 词：肌萎缩侧索硬化 SOD1基因 突变 

分 类 号：R744[医药卫生—神经病学与精神病学]