摘要
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 con-formation polymorphism,PCR- SSCP)结合 DNA序列分析方法 ,对 2 2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 2 2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 T12 5 8A和 A12 93G,外显子 14的16 6 7del ACT或 16 6 8del CTA或 16 6 9del TAC,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 ( T12 5 8A) ,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
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.
出处
《中华医学遗传学杂志》
EI
CAS
CSCD
2003年第3期177-180,共4页
Chinese Journal of Medical Genetics
基金
国家 8 63计划项目 (2 0 0 1 AA2 2 70 1 1 )
国家自然科学基金(30 0 70 2 73
3990 0 0 4 7)~~
