遗传性痉挛性截瘫spastin、atlastin和paraplegin基因突变分析  

Analysis on mutations of spastin,atlastin and paraplegin genes in Chinese patients with hereditary spastic paraplegia

作　　者：严新翔[1] 赵国华[1] 唐北沙[1] 刘小民[1] 沈璐[1] 陈昕[1] 胡正茂[2] 任志军[1] 夏昆[2] 

机构地区：[1]中南大学湘雅医院神经内科,长沙410008 [2]中南大学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11期683-685,共3页Chinese Journal of Neurology

基　　金：国家自然科学基金资助项目(30300199);国家"863"计划资助项目(2004AA227040)

摘　　要：目的探讨遗传性痉挛性截瘫(HSP)spastin、atlastin和parap legin基因的突变特点。方法应用聚合酶链反应-单链构象多态性(PCR-SSCP)结合DNA序列分析方法对24个常染色体显性遗传HSP家系和14例散发患者进行spastin基因和atlastin基因突变分析;对12个常染色体隐性遗传HSP家系和14例散发患者进行parap legin基因突变分析。结果在5个不同的常染色体显性遗传HSP家系中发现4个spastin基因新突变(1223 insCTCA、1258T→A,1293A→G和1668delCTA),在2例散发患者中发现2个spastin基因多态(IVS1-31C→G和IVS2-47A→G);在常染色体显性遗传HSP家系和散发患者中未发现atlastin基因突变或多态;在常染色体隐性遗传HSP家系和散发患者中未发现致病突变,仅在2例散发患者中发现2个parap legin基因多态(2063G→A及2066G→A)。结论我国遗传性痉挛性截瘫患者中spastin基因突变较常见,atlastin和parap legin基因的突变率可能较低。Objective To detect the mutations of spastin, atlastin and paraplegin genes in Chinese patients with hereditary spastic paraplegia （HSP）. Methods Mutation analysis of the spastin and atlastln genes in 24 autosomal dominant HSP families and 14 sporadic cases and the paraplegin gene in 12 autosomal recessive HSP families and 14 sporadic cases was carried out by polymerase chain reaction and single strand conformation polymorphism （PCR-SSCP） combined with direct sequencing. Results Four novel different mutations of the spastin gene were identified （1223insCTCA, 1258T→A, 1293A→G and 1668delCTA） in five autosomal dominant families, while t^o polymorphisms in the spastin gene （IVSI-31C→G and IVS2-47A→G） were identified in two sporadic cases. No disease-causing mutation and polymorphism of the atlastin gene was detected in the autusomal dominant families and sporadic cases. No disease-causing mutation of the paraplegin gene was detected, while two polymorphisms （2063G→A and 2066G→A） were detected in two sporadic cases. Conclusion Mutation of the spastin gene should be most common in Chinese HSP patieots. And the mutation of the atlastin and paraplegin might not be common.

关 键 词：痉挛性截瘫 遗传性 钙结合蛋白质类 GTP磷酸水解酶类 金属内肽酶类 突变 

分 类 号：R741[医药卫生—神经病学与精神病学]