PARKIN, PINK1, and DJ1 analysis in early-onset Parkinson's disease in Ireland

Background: Variants in PARKIN, PINK1, and DJ1 are associated with early-onset Parkinson' disease (EOPD, age-at-onset < 45). We previously reported a single PINK1 and a single DJ1 heterozygous variant carrier.

Purpose: We aimed to expand upon our previous EOPD studies and investigate for any genotype-phenotype correlations in Irish PD.

Methods: Three hundred fourteen PD patients were recruited from Dublin Neurological Institute, Ireland. Genetic analysis was performed at the Mayo Clinic, Jacksonville, USA. We screened 81 patients with young-onset PD (age-at-onset < 50), of which 58 had EOPD.

Results: We identified 4 patients with homozygous/compound heterozygous variants and 3 heterozygote carriers (pathogenic PINK1/DJ1 variants were not found). Expansion of one of the pedigrees showed a novel variant in exon 9, in a symptomatic patient. We identified 6.89% PARKIN variant carriers associated with EOPD.

Conclusion: These findings suggest that PINK1 and DJ1 are rarely associated with Irish YOPD, while PARKIN variant frequency is similar to that reported worldwide.