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 SCP 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.