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A multiethnic series of patients with early-onset Parkinson's disease (EOP) was studied to assess the frequency and nature of parkin/PARK2 gene mutations and to investigate phenotype-genotype relationships. Forty-six EOP probands with an onset age of < 45 years, and 14 affected relatives were ascertained from Italy, Brazil, Cuba, and Turkey. The genetic screening included direct sequencing and exon dosage using a new, cost-effective, real-time polymerase chain reaction method. Mutations were found in 33% of the indexes overall, and in 53% of those with family history compatible with autosomal recessive inheritance. Fifteen parkin alterations (10 exon deletions and five point mutations) were identified, including four novel mutations: Arg402Cys, Cys418Arg, IVS11-3C > G, and exon 8-9-10 deletion. Homozygous mutations, two heterozygous mutations, and a single heterozygous mutation were found in 8, 6, and 1 patient, respectively. Heterozygous exon deletions represented 28% of the mutant alleles. The patients with parkin mutations showed significantly earlier onset, longer disease duration, more frequently symmetric onset, and slower disease progression than the patients without mutations, in agreement with previous studies. This study confirms the frequent involvement of parkin and the importance of genetic testing in the diagnostic work-up of EOP.

Original publication

DOI

10.1002/mds.20343

Type

Journal article

Journal

Mov Disord

Publication Date

04/2005

Volume

20

Pages

424 - 431

Keywords

Adolescent, Adult, Age of Onset, Aged, Cost-Benefit Analysis, Exons, Female, Gene Library, Genotype, Humans, Intracellular Signaling Peptides and Proteins, Male, Mass Screening, Middle Aged, Oncogene Proteins, Parkinson Disease, Phenotype, Point Mutation, Polymerase Chain Reaction, Protein Deglycase DJ-1, Protein Kinases, Ubiquitin-Protein Ligases