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Mutations in the PINK1gene (PARK6),a putative serine‐threonine kinase, cause autosomal recessive Parkinson's disease. PINK1 functions as a protein kinase and confers protective effects in the mitochondria, where it is primarily located. We assessed in a population of European ancestry whether common genetic variation in this novel gene influences nonmendelian forms of Parkinson's disease. We defined the linkage disequilibrium structure of PINK1and used this to identify a set of tagging single nucleotide polymorphisms that we estimate will efficiently represent all of the common DNA variation in the entire gene. Genotyping these tags in a set of 576 Parkinson's disease patients and 514 controls did not demonstrate a case–control partition for allele or for haplotype and thus provides evidence against the existence of a common functional variants in PINK1that has a strong influence on PD risk. Ann Neurol 2004;56:329–335

A functional −1021C → T polymorphism in the dopamine β‐hydroxylase gene has been demonstrated to regulate plasma DBH activity. We report that individuals with genetically determined low serum DBH activity (genotype T/T) have protection against Parkinson's disease (p= 0.01). In particular, we observed an underrepresentation of the T/T genotype odds ratio = 0.46 (CI = 0.27‐0.8). Rather than identifying a haplotype, or a marker in linkage disequilibrium with the risk variant, this to our knowledge is the first report directly linking PD susceptibility with a proven functional variant. Ann Neurol 2004

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‐1mutations and determine their contribution in young‐onset and more typical later onset Parkinson's disease (PD). The entire open reading frame of the DJ‐1gene 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‐1mutations 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‐1mutations 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‐1mutations may only rarely contribute to the cause of this more typical sporadic form of the disease.

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.