常染色体隐性遗传早发性帕金森综合征致病基因的突变分析  

Mutation analysis of genes associated with autosomal recessive in early-onset parkinsonism

作　　者：严新翔[1] 张玉虎[1] 郭纪锋[1] 李静[1] 夏昆[2] 蔡芳[2] 潘乾[2] 龙志高[2] 陈涛[1] 曹立[1] 沈璐[1] 江泓[1] 赵国华[1] 唐北沙[1] 

机构地区：[1]中南大学湘雅医院神经内科,长沙410008 [2]中国医学遗传学国家重点实验室

出　　处：《中华神经科杂志》2005年第6期351-354,共4页Chinese Journal of Neurology

基　　金：国家"863"计划资助项目(2004AA227040);国家科技攻关计划资助项目(2002BA711A07-03);国家自然科学基金项目资助项目(30070273);高等学校博士学科点专项科研基金资助项目(20020533024)

摘　　要：目的研究常染色体隐性遗传早发性帕金森综合征(autosomalrecessiveearly-onsetparkinsonism,AREP)parkin、PINK1及DJ-1基因的突变。方法应用聚合酶链反应、DNA直接测序和限制性核酸内切酶酶切等技术对15个AREP家系进行parkin、PINK1及DJ-1基因的突变分析。结果在3个家系中发现parkin基因3个杂合突变,分别为202-203delAG和新发现的1069-1074delGTGTCC与T1422C突变。在2个家系中发现2个新的PINK1基因突变,分别为C938T及C1474T。未见DJ-1基因突变。3个PARK2家系平均发病年龄(25·2±5·7)岁,临床上肌张力障碍、姿势不稳、腱反射活跃、症状晨轻暮重常见,对多巴制剂反应好,左旋多巴诱导的运动障碍常见;2个PARK6家系平均发病年龄(25·8±10·0)岁,临床特征与PARK2相似,但未见肌张力障碍、姿势不稳及左旋多巴诱导的运动障碍。结论parkin、PINK1基因突变是AREP的常见病因;DJ-1在我国AREP中可能罕见;PARK2和PARK6具有相似临床表现,但均具有临床异质性。Objective To investigate the mutation of parkin,PINK1 and DJ-1 gene in Chinese patients with autosomal recessive early-onset parkinsonism (AREP). Methods Parkin,PINK1 and DJ-1 gene mutations were detected using polymerase chain reaction, DNA sequence analyses, and restriction enzyme digestion analysis in 15 AREP families. Results Three heterozygous parkin mutations (202-203delAG in exon 2, 968-973delGTGTCC in exon 9,T1422C in exon 12) were detected in three families. Two of the mutations (968-973delGTGTCC and T1422C) were not reported previously. Two novel point mutations (C938T in exon 4 and C1474T in exon 7) were found in PINK1 gene in two other families. There were no mutations in DJ-1 gene in these families. In the three PARK2 families, mean age at onset was 25.2±5.7 years. The clinical features of dystonia, postural instability, hyperreflexia, diurnal fluctuations with sleep benefit, good response to levodopa and L-dopa-induced dyskinesia were noted. In the two PARK6 families, mean age at onset was 25.8±10.0 years; their clinical features were similar to those of PARK2, but without dystonia, postural instability and L-dopa-induced dyskinesia. Conclusion Parkin and PINK1 gene mutations should be a common cause in Chinese patients with AREP. DJ-1 gene mutations are rare. PARK2 and PARK6 should have the similar clinical features, but all have clinical heterogeneity.

关 键 词：常染色体隐性遗传 帕金森综合征 突变分析 早发性 致病基因 parkin 限制性核酸内切酶 DNA直接测序 肌张力障碍 聚合酶链反应 基因突变 发病年龄 运动障碍 左旋多巴 腱反射活跃 方法应用 多巴制剂 临床特征 常见病因 临床表现 

分 类 号：R742.5[医药卫生—神经病学与精神病学]