The Studies On Parkin Gene Of Patients With Early-onset Parkinson Disease In GuangXi

Objective:To study the Parkin gene deletion mutations of exons 1 to 12 and the polymorphism of Parkin in the GuangXi patients with early-onset Parkinson disease.To analyze the association between these changes and the etiology in the disease.Methods:The Parkin gene's exons of 29 early-onset Parkinson patients,34 late-onset Parkinson patients and some of their relatives were amplified by polymerase chain reaction(PCR).The deletion mutations and point mutations of the exons were identified by agarose gel electrophoresis and single strand conformation polymorphism(SSCP).And in the samples with abnormal SSCP result,further sequencing was performed to confirm the mutation and its location.The Parkin gene's exons of two patients from each pedigree were sequenced.If an abnormal sequencing result was found,the exons of other members would be detected by dot blotting,radiant developing.Exon 4 and exon 10 of 57 sporadic parkinson disease patients and 110 healthy controls were amplified by PCR.Then the exons were digested by restriction fragment length polymorphism(RFLP)to observe polymorphism at S/N167,R/W366,V/L380.Results:We found no deletion mutations of the exons in all the patients and the controls.However,a new silent heterozygosis point mutation C869T in exon 7 was identified in 2 patients and 1 family without symptoms in a pedigree. But this mutation did not make a change in the sequence of the protein.In the late-onset parkinson disease genealogy,we found a new missense heterozygosis point mutation G1465T.This mutation led a change that a leucine took the place of arginine in the protein.The mutation appeared in 3 patients and their lineal families.A patient who was their cousinly did not have this mutation.The V/L380 frequency was significantly higher in EOPD group than the young control(X~2=4.232,P＜0.05).The frequency was also significantly higher in female Parkinson patients than the female control(X~2=6.055,P＜0.05).There were no significant differences in other two alleles.Conclusions:Our finding suggests that in Guangxi the deletion mutations and polymorphism at S/N167,R/W366 in Parkin gene might not be a susceptible factor for EOPD patients.Point mutation in exon 7 and polymorphism at V/L380 of Parkin might be related to EOPD patients.The mutation rate of Parkin exons in Guangxi was relatively low.The clinical features in patients with Parkin mutations included early onset,slow disease progression,rigidity,and good response to levodopa.