Dataset Information

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

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.

SUBMITTER: Olszewska DA

PROVIDER: S-EPMC9376961 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Olszewska Diana A DA McCarthy Allan A Soto-Beasley Alexandra I AI Walton Ronald L RL Ross Owen A OA Lynch Tim T

Irish journal of medical science 20210322 2

<h4>Background</h4>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.<h4>Purpose</h4>We aimed to expand upon our previous EOPD studies and investigate for any genotype-phenotype correlations in Irish PD.<h4>Methods</h4>Three hundred fourteen PD patients were recruited from Dublin Neurological Institute, Ireland. Genetic analysis was performed at the M ...[more]

PMID: 33751372

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Project description:While early-onset Parkinson's disease (EOPD) caused by mutations in the parkin gene (PRKN) tends to have a relatively benign course compared to genetically undetermined (GU)-EOPD, the exact underlying mechanisms remain elusive. We aimed to search for the differences between PRKN-EOPD and GU-EOPD by dopamine transporter (DAT) and glucose metabolism positron-emission-tomography (PET) imaging. Twelve patients with PRKN-EOPD and 16 with GU-EOPD who accepted both 11C-2b-carbomethoxy-3b-(4-trimethylstannylphenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose PET were enrolled. The 11C-CFT uptake was analyzed on both regional and voxel levels, whereas glucose metabolism was assessed in a voxel-wise fashion. Correlations between DAT and glucose metabolism imaging, DAT imaging and clinical severity, as well as glucose metabolism imaging and clinical severity were explored. Both clinical symptoms and DAT-binding patterns in the posterior putamen were highly symmetrical in patients with PRKN-EOPD, and dopaminergic dysfunction in the ipsilateral putamen was severer in patients with PRKN-EOPD than GU-EOPD. Meanwhile, the DAT binding was associated with the severity of motor dysfunction in patients with GU-EOPD only. Patients with PRKN-EOPD showed increased glucose metabolism in the contralateral medial frontal gyrus (supplementary motor area (SMA)), contralateral substantia nigra, contralateral thalamus, and contralateral cerebellum. Notably, glucose metabolic activity in the contralateral medial frontal gyrus was inversely associated with regional DAT binding in the bilateral putamen. Patients with PRKN-EOPD showed enhanced metabolic connectivity within the bilateral putamen, ipsilateral paracentral and precentral lobules, and the ipsilateral SMA. Collectively, compared to GU-EOPD, PRKN-EOPD is characterized by symmetrical, more severe dopaminergic dysfunction and relative increased glucose metabolism. Meanwhile, SMA with elevated glucose metabolism and enhanced connectivity may act as compensatory mechanisms in PRKN-EOPD.Supplementary informationThe online version contains supplementary material available at 10.1007/s43657-022-00077-8.

Dataset Information

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

Background

Purpose

Methods

Results

Conclusion

Publications

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

Similar Datasets

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