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Abstract

Mutations in DJ-1 (PARK7) have been reported in two consanguineous families with young-onset Parkinson's disease (YOPD). This study aims to confirm the presence of pathogenic DJ-1 mutations and determine their contribution in young-onset and more typical later onset Parkinson's disease (PD). The entire open reading frame of the DJ-1 gene was screened by direct sequencing in 185 unrelated YOPD patients and a separate cohort of 190 pathologically proven cases of PD. Ethnically matched controls were screened for all mutations identified. We report a low frequency of pathogenic DJ-1 mutations in our cohort of patients. One homozygous missense mutation and one heterozygous mutation were found in two YOPD samples. In addition, several variants were found in the coding sequence of the gene, which are likely to represent polymorphisms. In one case, the polymorphism was population specific. The reported 14Kbp deletion was not found in any of our samples or controls. We confirm the presence of pathogenic DJ-1 mutations in YOPD and estimate their frequency at approximately 1%. No mutations were found in our cohort of later onset sporadic pathologically confirmed cases, suggesting that DJ-1 mutations may only rarely contribute to the cause of this more typical sporadic form of the disease.