title: Parkinson's disease in Ireland: clinical presentation and genetic heterogeneity in patients with parkin mutations.
abstract: Early-onset autosomal recessive parkinsonism is associated with parkin gene mutations. Different parkin mutations occur in many ethnic backgrounds; however, the phenotype may vary. We studied 102 young-onset (age at onset <60 years) Parkinson's disease (PD) patients. From 102 patients, 40 with early-onset PD (<45 years at symptomatic onset) were selected for clinical assessment and parkin gene molecular analysis for duplications/deletions and point mutations. We identified parkin mutations in 7 of 40 early-onset patients; including novel compound heterozygotes and potential splice site changes. The mean age at onset in the 7 parkin mutation-positive patients was 33 +/- 9 years (age range, 18-42 years), marginally lower than that of the 33 parkin-negative early-onset patients, 38 +/- 7 years (age range, 17-45 years). A family history of PD was present in 4 of 7 patients with parkin mutations, compared with 6 of 33 early-onset parkin-negative patients. Overall, parkin mutations were found in 4 of 10 patients with a positive family history and 3 of 30 patients without a family history of PD. Patients with parkin mutations had more dystonia, dyskinesia, and sleep benefit compared with parkin-negative patients. We subsequently identified a single point mutation among the 62 young-onset (age at onset 45 to <60 years). Mutations in the parkin gene may account for approximately 17% of early-onset (age at onset <45 years) parkinsonism in Ireland, in agreement with previous European studies.
authors.affiliation: University College Dublin Conway Institute of Biomolecular and Biomedical Research, Department of Neurology, Mater Misericordiae Hospital, Ireland.
authors.forename: Joseph
authors.initials: J
authors.lastname: Wiley
authors.forename: Timothy
authors.initials: T
authors.lastname: Lynch
authors.forename: Sarah
authors.initials: S
authors.lastname: Lincoln
authors.forename: Lisa
authors.initials: L
authors.lastname: Skipper
authors.forename: Mary
authors.initials: M
authors.lastname: Hulihan
authors.forename: David
authors.initials: D
authors.lastname: Gosal
authors.forename: Gina
authors.initials: G
authors.lastname: Bisceglio
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kachergus
authors.forename: John
authors.initials: J
authors.lastname: Hardy
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Farrer
mesh_terms: D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D018740:Genetic Heterogeneity; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology; D017354:Point Mutation / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein