Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort

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Vollstedt, Eva-Juliane
Schaake, Susen
Lohmann, Katja
Padmanabhan, Shalini
Brice, Alexis
Lesage, Suzanne
Tesson, Christelle
Vidailhet, Marie
Wurster, Isabel
Hentati, Faycel
Mirelman, Anat
Giladi, Nir
Marder, Karen
Waters, Cheryl
Fahn, Stanley
et al.
Griffith University Author(s)
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2023
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Abstract

Background: As 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. Objective: The 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. Methods: We 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. Results: We 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. Conclusions: Within 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.

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Movement Disorders

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38

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2

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© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Clinical sciences

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Life Sciences & Biomedicine

Clinical Neurology

Neurosciences & Neurology

Parkinson's disease

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Vollstedt, E-J; Schaake, S; Lohmann, K; Padmanabhan, S; Brice, A; Lesage, S; Tesson, C; Vidailhet, M; Wurster, I; Hentati, F; Mirelman, A; Giladi, N; Marder, K; Waters, C; Fahn, S; et al., Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort, Movement Disorders, 2023, 38 (2), pp. 286-303

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