三个常染色体隐性遗传性青少年型帕金森综合征家系的基因型与表型分析  

Genotype and phenotype analyses of three families with autosomal recessive juvenile parkinsonism

作　　者：郭纪锋[1] 唐北沙[1] 张玉虎[1] 刘洪建[2] 严新翔[1] 陈涛[1] 沈璐[1] 江泓[1] 夏昆[3] 蔡芳[3] 潘乾[3] 

机构地区：[1]中南大学湘雅医院神经内科,长沙410001 [2]滨州医学院附属医院胸心外科 [3]中国医学遗传学国家重点实验室

出　　处：《中华医学遗传学杂志》2006年第1期70-73,共4页Chinese Journal of Medical Genetics

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

摘　　要：目的探讨常染色体隐性遗传性青少年型帕金森综合征（autosomal recessive iuvenile parkinsonism，AR-JP）parkin基因的突变及临床特征。方法应用聚合酶链反应、DNA测序和限制性核酸内切酶酶切等技术对15个AR—JP家系先证者的parkin基因进行突变研究。结果发现3个家系有parkin基因的突变，其中2个家系含parkin基因的杂合缺失突变，分别为第2外显子的202—203delAG及第9外显子的1069-1074delGTGTCC；另一家系发现一个杂合点突变，为第12外显子的1422（T→C）。其中1069—1074delGTGTCC和1422（T→C）为新的突变。3个家系共6名患者，发病年龄18～31岁，平均25．2±5．7岁；病情进展慢，腱反射活跃或亢进、症状波动常见；对小剂量多巴制剂反应良好。结论我国的AR-JP家系存在parkjn基因的突变；含parkin基因突变的AR—JP患者有帕金森病的一般临床表现．又有其独特的临床特征。Objective To investigate the gene mutations and the clinical features of Chinese patients with autosomal recessive juvenile parkinsonism（ AR-JP）. Methods the polymerase chain reaction（PCR）, DNA sequence analysis, and restriction enzyme digestion analysis were applied to check parkin gene mutations of 15 index patients from 15 families with AR-JP. Results Three families were detected to have parkin mutations. Two of them had heterozygous deletion mutations （202-203 del AG in exon 2, 1069-1074 del GTTCC in exon 9） and another of them carried a heterozygous missense mutation [1422（T→C） in exon 12]. Two of the mutations [ 1069-1074delGTGTCC and 1422（T→ C） ] were not reported previously. There were six patients in the three families. Mean age at onset was 25.2±5.7 years, ranging from 18 to 31 years. The symptoms were under slow progression, diurnal fluctuation with sleep benefit, and hyperreflexia were relatively prominent. Response to levodopa was satisfactory. Conclusion There are parkin mutations happened in Chinese patients with AR-JP. Patients with parkin mutations have distinct clinical features besides the common clinical features of Parkinson＇ s disease.

关 键 词：常染色体隐性遗传性青少年型帕金森综合征 PARKIN基因 基因突变 表型分析 

分 类 号：R742.5[医药卫生—神经病学与精神病学] R774.13[医药卫生—临床医学]