Objective': To screen for exonic and point mutations in the Parkin gene in both Chinese and American Caucasian younger onset Parkinson's disease (YOPD) patients.Background: Recently, the Autosomal recessive ju...Objective': To screen for exonic and point mutations in the Parkin gene in both Chinese and American Caucasian younger onset Parkinson's disease (YOPD) patients.Background: Recently, the Autosomal recessive juvenile parkinsonism (ARJP) gene was first mapped to chromosome 6q25.2-27 and was late cloned and designated as Parkin. A wide variety of mutations, including homozygous exonic deletions and point mutations,have been found in at least more than 50 ARJP families of Japanese, European and Jewish origins. However, the distribution of Parkin gene mutations is not known in the Chinese and American Caucasians, It is also not clear how frequent the Parkin gene mutations occur in YOPD patients. Method and Material: Twenty-one Chinese subjects were selected from 121 Chinese PD inpatients who were admitted to the Xuanwu Hospital in Beijing between August of 1998 and April of 1999 and had an onset before age 51. Thirty-eight American subjects were PD patients with an onset before age 41 from the Tissue Bank of the Parkinson′s Institute at California. Homozygous exonic deletion and point mutations in all 12 exons of the Parkin gene were screened using PCR, SSCP and direct sequencing methods. Mutations identified by sequencing were further confirmed by restriction enzyme digestion. Results: Five different types of homozygous deletion mutations (exons 1, 4, 6, 7 and 12) were found in 7 out of 21 Chinese cases but none of the 37 American Caucasian patients in all 12 exons of Parkin gene. One novel and four polymorphic mutationswere found in the American Caucasian YOPD cases.Conclusion: our results suggest that homozygous exonic deletions in the Parkin gene may account for a significant amount of YOPD in the Chinese but not in the American Caucasian YOPD.展开更多
文摘Objective': To screen for exonic and point mutations in the Parkin gene in both Chinese and American Caucasian younger onset Parkinson's disease (YOPD) patients.Background: Recently, the Autosomal recessive juvenile parkinsonism (ARJP) gene was first mapped to chromosome 6q25.2-27 and was late cloned and designated as Parkin. A wide variety of mutations, including homozygous exonic deletions and point mutations,have been found in at least more than 50 ARJP families of Japanese, European and Jewish origins. However, the distribution of Parkin gene mutations is not known in the Chinese and American Caucasians, It is also not clear how frequent the Parkin gene mutations occur in YOPD patients. Method and Material: Twenty-one Chinese subjects were selected from 121 Chinese PD inpatients who were admitted to the Xuanwu Hospital in Beijing between August of 1998 and April of 1999 and had an onset before age 51. Thirty-eight American subjects were PD patients with an onset before age 41 from the Tissue Bank of the Parkinson′s Institute at California. Homozygous exonic deletion and point mutations in all 12 exons of the Parkin gene were screened using PCR, SSCP and direct sequencing methods. Mutations identified by sequencing were further confirmed by restriction enzyme digestion. Results: Five different types of homozygous deletion mutations (exons 1, 4, 6, 7 and 12) were found in 7 out of 21 Chinese cases but none of the 37 American Caucasian patients in all 12 exons of Parkin gene. One novel and four polymorphic mutationswere found in the American Caucasian YOPD cases.Conclusion: our results suggest that homozygous exonic deletions in the Parkin gene may account for a significant amount of YOPD in the Chinese but not in the American Caucasian YOPD.
