中国人遗传性痉挛性截瘫spastin基因突变研究

目的 探讨中国人遗传性痉挛性截瘫（hereditary spastic paraplegia,HSP)spastin基因的突变特点，为该病的基因诊断提供依据。方法 应用聚合酶链反应—单链构象多态性(PCR—single strand conformation polymorphism，PCR—SSCP)结合DNA序列分析方法，对22个常染色体显性遗传HSP家系的先证者和9例散发性HSP患者的spastin基因进行研究，对发现异常SSCP条带的家系内成员进行突变研究。结果 在22例常染色体显性遗传HSP家系的先证者和9例散发性HSP患者中发现异常SSCP条带6例，进行DNA序列分析，共发现3种spastin基因突变，为外显子8的T1258A和A1293G，外显子14的1667delACT或1668delCTA或1669delTAC，均未见报道，突变位点均位于spastin基因功能区域，其中两个家系存在同一种突变(T1258A)，各突变家系内患者存在同样的异常SSCP条带。结论 中国人遗传性痉挛性截瘫患者存在spastin基因突变，该基因在中国人常染色体显性遗传的遗传性痉挛性截瘫家系中的突变率较低(18．2％)，点突变是主要的突变形式，外显子8可能是中国人spastin基因的突变热点。

Spastin gene mutation in Chinese patients with hereditary spastic paraplegia

Objective To investigate the mutation characteristics of spastin gene in Chinese patients with hereditary spastic paraplegia(HSP) and thus provide a basis for the gene diagnosis of HSP. Methods Mutation of spastin gene was screened by polymerase chain reaction single strand conformation polymorphism(PCR SSCP) combined with DNA direct sequencing in 31 unrelated affected HSP individuals in China, of whom 22 were from autosomal dominant families and 9 were sporadic HSP patients. Co segregation analysis was carried out after the finding of abnormal SSCP bands. Results Six cases were found to have abnormal SSCP bands, and among them, two missense mutations (T1258A, A1293G in exon 8) and one deletion mutation(1667delACT or 1668delCTA or 1669delTAC in exon 14) were found and all of them were not reported previously. They were all co segregated with the disease and were localized within the functional domain of spastin gene. Besides, T1258A was seen in two unrelated families. Conclusion The mutation rate (18.2%) in autosomal dominant HSP in Chinese patients is comparatively low. Point mutation is the major mutation type and exon 8 may be the mutation hot spot.