Screening PARK genes for mutations in early-onset Parkinson's disease patients from Queensland, Australia

Parkinsonism Relat Disord. 2009 Feb;15(2):105-9. doi: 10.1016/j.parkreldis.2007.11.016. Epub 2008 May 19.

Abstract

A family history of Parkinson's disease (PD) is the most commonly reported risk factor after age, suggesting a genetic component to the disease in a sub-group of patients. Mutations in at least six genes have been identified that can lead to monogenic forms of PD. We screened a sample of 74 early-onset PD cases out of a cohort of 950 patients (onset <50 years) for genetic abnormalities in known familial Parkinsonism genes. A self-reported family history of PD existed for 30 patients (40.5%). Of these, 13 each had a first- or a second-degree relative with PD and four reported a more distant relative with PD. The entire coding region of the PRKN (MIM 602544), DJ-1 (MIM 602533) and PINK1 (MIM 698309) genes, and exon 41 of the LRRK2 gene (MIM 609007) were screened by direct sequencing. All exons of PRKN were examined for gene-dosage abnormalities. Screening identified five patients with putative genetic disease: two patients carried PRKN mutations (p.G12R heterozygous and p.G430D homozygous), one patient carried a p.G411S heterozygous amino acid change in the PINK1 gene and two individuals were heterozygous for the common p.G2019S mutation in LRRK2. No alpha-synuclein or DJ-1 variants were observed. Our data suggest that approximately 7% of early-onset PD cases seen in Queensland movement disorders clinics have mutations involving known PARK genes.

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • DNA Mutational Analysis / methods
  • Exons / genetics
  • Female
  • Genetic Testing / methods
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Oncogene Proteins / genetics
  • Parkinson Disease / genetics*
  • Protein Deglycase DJ-1
  • Protein Kinases / genetics*
  • Protein Serine-Threonine Kinases / genetics
  • Queensland
  • Ubiquitin-Protein Ligases / genetics*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Oncogene Proteins
  • Ubiquitin-Protein Ligases
  • parkin protein
  • Protein Kinases
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • PTEN-induced putative kinase
  • Protein Serine-Threonine Kinases
  • PARK7 protein, human
  • Protein Deglycase DJ-1