Prevalence of parkin gene mutations and variations in idiopathic Parkinson's disease

Mutations in the parkin gene are a common cause of autosomal recessive juvenile parkinsonism (AR-JP) but their role in idiopathic Parkinson's disease (PD) is not clear. Recent studies demonstrate that most young onset PD without family history is not due to mutations in parkin. However, there is less information about the role of this gene in older onset PD. The objective of the present study was to evaluate the prevalence and frequency of parkin gene mutations and variations in the general population of patients with PD categorized on the basis of family history and age of onset. We sequenced a sample of 50 familial PD patients, screened a sample of 429 PD patients, and 115 normal controls for the previously reported mutations, deletions, single nucleotide polymorphisms (SNP) in exons 2-12 of the parkin gene, and performed RT-PCR of exon 1. A total of two heterozygous mutations in exon 7 (R275W; 0.2%) were detected in the PD group, but none were found in controls. No mutation or deletion was observed in exons 2, 3, 5, 6, 8, 9 or 12. There was also no deletion or duplication of exon 1. The SNPs in exon 4, 10, and 11 that cause amino acid changes were very rare (1-5%). We did not find the exon 4 variation in the controls while allele frequencies were similar among PD patients and controls in exon 10 and 11 polymorphisms. Mutations were not associated with a positive family history of PD or younger age of onset. We concluded that no new mutation, nor the previously described parkin polymorphisms or known mutations, are playing any direct role in the development of PD in this group of PD patients.