中国华东地区家族性肌萎缩侧索硬化_省略_od1基因突变检测及临床特点分析_陈嬿.pdfVIP

中国临床神经科学 2016 年第 24 卷第 2 期 ·146· Chin J Clin Neurosci 2016, 24 (2), 146~152 论 著 SOD1 陈 嬿，董 漪，卢家红，刘丰韬，蒋雨平，邬剑军 (复旦大学附属华山医院神经内科 200040) 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 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(SOD 1) 的基因突变筛查。 　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 方法 DNA 直接测序法对外周血DNA 进行SOD 1 基因5 个外显子的突变筛查，并分析SOD 1 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SOD 1 突变。其中3 例为位于2 号外显子的已知错义突变p.His46Arg(c.140AG) ， 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.143TC) ，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.112GC) ，单侧上肢远端起病，上下运动神经元均受损，进展缓慢。 　中国华东地区FALS 患者中 结论 SOD 1 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。 Screening of Mutations in SOD 1 Gene and Aanalysis of Clinical Features of Patients with Familiar Amyotrophic Lateral Sclerosis in East China CHEN Yan, DONG Yi, LU Jia-hong, LIU Feng-tao, JIANG Yu-ping, WU Jian-jun Department of Neurology, Huashan Hospital, Fudan University, Shanghai 200040, China KEY WORDS　familiar amyotrophic lateral sclerosis; SOD 1 gene; mutation; phenotype ABSTRACT 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. SOD 1 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