title: Detection of Parkin (PARK2) and DJ1 (PARK7) mutations in early-onset Parkinson disease: Parkin mutation frequency depends on ethnic origin of patients.
abstract: Mutations in the Parkin (PARK2) and the DJ1 (PARK7) gene cause early-onset Parkinson disease (EOPD). We tested 75 Serbian EOPD patients for mutations in both genes by conventional mutational screening (SSCP/dHPLC/sequencing) to detect small sequence alterations and by gene dosage studies (quantitative PCR) to reveal deletions or multiplications of one or more exons. A compound heterozygous Parkin mutation (exon deletion and point mutation; [c.836_972del]+[c.1411C>T]; +1 is first nucleotide of GenBank AB009973.1) was identified in a patient who showed a relatively benign course after a disease onset at 41 years. Another case had a heterozygous exon deletion in DJ1 ([c.253_322del]+[?]) and presented with an age at onset of 45 years and a rapid disease course. In conclusion, Parkin mutations are surprisingly rare in our Serbian EOPD sample, suggesting that the mutation rate depends on the ethnic origin of the patients. Although DJ1 mutations appear to be rare, we confirm their role in EOPD and demonstrate the importance of gene dosage studies.
authors.affiliation: Department of Human Genetics, University of Lübeck, Lübeck, Germany.
authors.forename: Ana
authors.initials: A
authors.lastname: Djarmati
authors.forename: Katja
authors.initials: K
authors.lastname: Hedrich
authors.forename: Marina
authors.initials: M
authors.lastname: Svetel
authors.forename: Nora
authors.initials: N
authors.lastname: Schäfer
authors.forename: Vladislava
authors.initials: V
authors.lastname: Juric
authors.forename: Slobodanka
authors.initials: S
authors.lastname: Vukosavic
authors.forename: Robert
authors.initials: R
authors.lastname: Hering
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Stanka
authors.initials: S
authors.lastname: Romac
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kostic
mesh_terms: D000328:Adult; D017668:Age of Onset; D004252:DNA Mutational Analysis; D005260:Female; D006579:Heterozygote; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D000071617:Protein Deglycase DJ-1; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D015022:Yugoslavia
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1