Analysis of the PINK1 gene in a large cohort of cases with Parkinson disease

Background Mutations in the PTEN-induced kinase ( PINK1 ) gene located within the PARK6 locus on chromosome 1p35-p36 have recently been identified in patients with recessive early-onset Parkinson disease. Objective To assess the prevalence of PINK1 mutations within a series of early- and late-onset Parkinson disease patients living in North America. Design All coding exons of the PINK1 gene were sequenced in a series of 289 Parkinson disease patients and 80 neurologically normal control subjects; the mutation frequencies were evaluated in additional controls (100 white and 50 Filipino subjects). Results We identified 27 variants, including the first reported compound heterozygous mutation (Glu240Lys and Leu489Pro) and a homozygous Leu347Pro mutation in 2 unrelated young-onset Parkinson disease patients. Conclusion Autosomal recessive mutations in PINK1 are a rare cause of young-onset Parkinson disease.