title: Screening PARK genes for mutations in early-onset Parkinson's disease patients from Queensland, Australia.
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.
authors.affiliation: Eskitis Institute for Cellular and Molecular Therapies, Griffith University, Nathan, Qld 4111, Australia. G.Mellick@griffith.edu.au
authors.forename: George D
authors.initials: GD
authors.lastname: Mellick
authors.forename: Gerhard A
authors.initials: GA
authors.lastname: Siebert
authors.forename: Manabu
authors.initials: M
authors.lastname: Funayama
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Buchanan
authors.forename: Yuanzhe
authors.initials: Y
authors.lastname: Li
authors.forename: Yoko
authors.initials: Y
authors.lastname: Imamichi
authors.forename: Hiroyo
authors.initials: H
authors.lastname: Yoshino
authors.forename: Peter A
authors.initials: PA
authors.lastname: Silburn
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons / Q000235:genetics; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics; D010300:Parkinson Disease / Q000235:genetics*; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011793:Queensland; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D015513:Oncogene Proteins; D000071617:Protein Deglycase DJ-1; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein; C495280:LRRK2 protein, human; C105131:PARK7 protein, human