Diana A Olszewska1,2,3, Allan McCarthy4,5, Owen A Ross6,7,8, Tim Lynch4,7, Alexandra I Soto-Beasley6, Ronald L Walton6. 1. The Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland. diana.angelika.olszewska@gmail.com. 2. Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA. diana.angelika.olszewska@gmail.com. 3. Health Affairs & School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. diana.angelika.olszewska@gmail.com. 4. The Dublin Neurological Institute at the Mater Misericordiae University Hospital, Dublin, Ireland. 5. Department of Neurology, The Adelaide and Meath Hospital, Dublin, Ireland. 6. Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA. 7. Health Affairs & School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. 8. Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL, USA.
Abstract
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.
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.
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