遗传性痉挛性截瘫SPG4和SPG3A基因突变和多态分析  

Mutation and polymorphism analysis of SPG4 and SPG3A in Chinese patients with hereditary spastic paraplegia

作　　者：赵坤[1] 吴志英[2] 王柠[1] 赵桂宪[2] 林珉婷[1] 慕容慎行[1] 

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

出　　处：《中华神经科杂志》2009年第4期253-257,共5页Chinese Journal of Neurology

基　　金：基金项目：福建医科大学教授学术发展基金资助项目（JS6036）;福建省高校创新团队培育计划资助项目（FMU-RT002）;复旦大学特聘教授华山医院配套基金资助项目

摘　　要：目的筛查并分析遗传性痉挛性截瘫（HSP）SPG4和SPG3A基因突变，了解中国人群这2个基因的突变特点。方法联合应用变性高效液相色谱分析（DHPLC）和DNA序列分析方法对24例常染色体显性遗传的HSP（AD—HSP）家系的先证者和32例散发性HSP患者进行SPG4和SPG3A基因突变筛查，对24例AD—HSP家系的先证者进一步直接测序筛查这2个基因的突变。结果在1个AD—HSP家系中发现1个位于SPG4基因上的新型突变1616＋1g→t杂合突变。在此家系中，共发现了3例现症患者和2例症状前患者。本组病例未检出SPG3A基因突变。此外，共发现了8种新的SPG4多态和3种新的SPG3A多态。结论本组检测结果丰富了SPG4和SPG3A基因的突变和多态库。这2个基因突变在本组病例中较少见，需要继续分析其他基因。Objective To screen the mutation and analysis its characteristics of SPG4 and SPG3A in Chinese patients with hereditary spastic paraplegia （HSP）. Methods Mutation and polymorphism of the SPG4 and SPG3A were screened in the index cases of 26 autosomal dominant families （AD-HSP） and 30 sporadic cases by combination of DHPLC and sequencing analysis, then the index cases of 26 AD-HSP were further confirmed with direct sequencing. Results One novel mutation of SPG4, 1616 ＋ lg→t, was identified in the index case from an AD-HSP family. Three symptomatic patients and 2 pre-symptomatic patients were found in this family by sequencing analysis. No mutation of SPG3A was detected. In addition, 8 novel SPG4 polymorphisms and 3 novel SPG3A polymorphisms were identified. Conclusions The study has broadened the mutation and polymorphism spectrums of SPG4 and SPG3A. Mutation of these two genes is less common in this group of patients.

关 键 词：痉挛性截瘫 遗传性 腺苷三磷酸酶类 GTP磷酸水解酶类 突变 多态观象 遗传多态 

分 类 号：R686[医药卫生—骨科学]