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AbstractBackgroundAs gene‐targeted therapies are increasingly being developed for Parkinson's disease (PD), identifying and characterizing carriers of specific genetic pathogenic variants is imperative. Only a small fraction of the estimated number of subjects with monogenic PD worldwide are currently represented in the literature and availability of clinical data and clinical trial‐ready cohorts is limited.ObjectiveThe objectives are to (1) establish an international cohort of affected and unaffected individuals with PD‐linked variants; (2) provide harmonized and quality‐controlled clinical characterization data for each included individual; and (3) further promote collaboration of researchers in the field of monogenic PD.MethodsWe conducted a worldwide, systematic online survey to collect individual‐level data on individuals with PD‐linked variants in SNCA, LRRK2, VPS35, PRKN, PINK1, DJ‐1, as well as selected pathogenic and risk variants in GBA and corresponding demographic, clinical, and genetic data. All registered cases underwent thorough quality checks, and pathogenicity scoring of the variants and genotype–phenotype relationships were analyzed.ResultsWe collected 3888 variant carriers for our analyses, reported by 92 centers (42 countries) worldwide. Of the included individuals, 3185 had a diagnosis of PD (ie, 1306 LRRK2, 115 SNCA, 23 VPS35, 429 PRKN, 75 PINK1, 13 DJ‐1, and 1224 GBA) and 703 were unaffected (ie, 328 LRRK2, 32 SNCA, 3 VPS35, 1 PRKN, 1 PINK1, and 338 GBA). In total, we identified 269 different pathogenic variants; 1322 individuals in our cohort (34%) were indicated as not previously published.ConclusionsWithin the MJFF Global Genetic PD Study Group, we (1) established the largest international cohort of affected and unaffected individuals carrying PD‐linked variants; (2) provide harmonized and quality‐controlled clinical and genetic data for each included individual; (3) promote collaboration in the field of genetic PD with a view toward clinical and genetic stratification of patients for gene‐targeted clinical trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
FOS: Computer and information sciences, Genetic testing, : Neurology [D14] [Human health sciences], Parkinson's disease, Monogenic PD, Clinical sciences, /dk/atira/pure/subjectarea/asjc/2700/2728, Parkinson's disease; monogenic PD, /dk/atira/pure/subjectarea/asjc/2800/2808, Gene, genetics [Parkinson Disease], Disease, Parkinson Disease/genetics, Human health sciences, Internal medicine, Parkinson's Disease, parkinson's disease; monogenic pd, monogenic PD, Cohort, Life Sciences, name=Clinical Neurology, Parkinson Disease, LRRK2, Neurology, Clinical neurology, Medicine, : Genetics & genetic processes [F10] [Life sciences], : Génétique & processus génétiques [F10] [Sciences du vivant], Life Sciences & Biomedicine, Research Article ; Research Articles ; Parkinson's disease ; monogenic PD, Nurr1/CoREST Pathway in Neuroprotection and Inflammation, Genotype, name=Neurology, Bioinformatics, Cognitive Neuroscience, Clinical Neurology, 610, Sciences de la santé humaine, Cellular and Molecular Neuroscience, Neurologie, Health Sciences, Parkinson's disease; Monogenic PD, Genetics, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biology, Parkin, Science & Technology, : Neurologie [D14] [Sciences de la santé humaine], PINK1, Neurosciences, Neurology - Radboud University Medical Center, Radboudumc 3: Disorders of movement DCMN: Donders Center for Medical Neuroscience, ta3124, Autism Spectrum Disorders, FOS: Biological sciences, Mutation, Neurosciences & Neurology, Human medicine, Neurology (clinical), Pathophysiology of Parkinson's Disease, Neuroscience, ddc: ddc:, ddc: ddc:610
FOS: Computer and information sciences, Genetic testing, : Neurology [D14] [Human health sciences], Parkinson's disease, Monogenic PD, Clinical sciences, /dk/atira/pure/subjectarea/asjc/2700/2728, Parkinson's disease; monogenic PD, /dk/atira/pure/subjectarea/asjc/2800/2808, Gene, genetics [Parkinson Disease], Disease, Parkinson Disease/genetics, Human health sciences, Internal medicine, Parkinson's Disease, parkinson's disease; monogenic pd, monogenic PD, Cohort, Life Sciences, name=Clinical Neurology, Parkinson Disease, LRRK2, Neurology, Clinical neurology, Medicine, : Genetics & genetic processes [F10] [Life sciences], : Génétique & processus génétiques [F10] [Sciences du vivant], Life Sciences & Biomedicine, Research Article ; Research Articles ; Parkinson's disease ; monogenic PD, Nurr1/CoREST Pathway in Neuroprotection and Inflammation, Genotype, name=Neurology, Bioinformatics, Cognitive Neuroscience, Clinical Neurology, 610, Sciences de la santé humaine, Cellular and Molecular Neuroscience, Neurologie, Health Sciences, Parkinson's disease; Monogenic PD, Genetics, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Biology, Parkin, Science & Technology, : Neurologie [D14] [Sciences de la santé humaine], PINK1, Neurosciences, Neurology - Radboud University Medical Center, Radboudumc 3: Disorders of movement DCMN: Donders Center for Medical Neuroscience, ta3124, Autism Spectrum Disorders, FOS: Biological sciences, Mutation, Neurosciences & Neurology, Human medicine, Neurology (clinical), Pathophysiology of Parkinson's Disease, Neuroscience, ddc: ddc:, ddc: ddc:610
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