一个肌萎缩侧索硬化家系的SOD1基因突变

肌萎缩侧索硬化 (amyotrophic lateral sclerosis,ALS)是一种以脑和脊髓中大的运动神经元变性为特征的神经系统变性疾病。 5 %～ 10 %的患者有家族性。临床表现为缓慢起病 ,进行性发展 ,逐渐出现四肢肌肉的无力、萎缩 ,伴锥体束征等。临床治疗非常困难。目前已肯定编码铜、锌超氧化物歧化酶 (Cu/ Zn superoxidedismutase,Cu/ Zn- SOD)的 SOD1基因突变可引起部分家族性 ALS的发病[1] 。我们对重庆地区一个具有特殊临床表型的 ALS家系进行了 SOD1基因检测 ,结果发现部分患者第 2和第 5外显子有明显异常。1　对象与方法1.1　对象　受…

Identification of the mutation of SOD1 gene in a familial amyotrophic lateral sclerosis

SHI Shu-gui, LI Lu-si, CHEN Kang-nin, LIU Xing. (Department of Neurology, Southwest Hospital, Third Military Medical University, Chongqing, 400038 P.R. China.) Objective To identify the mutation of Cu/Zn superoxide dismutase ( SOD1) gene in an amyotrophic lateral sclerosis (ALS) family with unique phenotype. Methods Five exons of SOD1 gene were amplified by PCR.The differences of these products were analyzed by PCR-single strand conformation polymorphism and visualized by silver staining. Results Abnormal bands were found in exons 2 and 5 of SOD1 gene in several familial members. DNA sequence analysis verified that a base pair insertion occurred in the codon area of exon 2 and in the intron area of exon 5. And the insertion mutation of exon 2 led to a frameshift mutation and premature stop. It is a new type of SOD1 mutation which may be associated with familial amyotrophic lateral sclerosis. Conclusion Insertion mutation of exon 2 may be responsible for the disease of an ALS family in Chongqing.