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

2

Issued Date

2023-02-01

Resource Type

Article

ISSN

08853185

eISSN

15318257

DOI

10.1002/mds.29288

Scopus ID

2-s2.0-85147202939

Pubmed ID

36692014

Journal Title

Movement Disorders

Volume

38

Issue

2

Start Page

286

End Page

303

Rights Holder(s)

SCOPUS

Bibliographic Citation

Movement Disorders Vol.38 No.2 (2023) , 286-303

Suggested Citation

Vollstedt E.J. Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort. Movement Disorders Vol.38 No.2 (2023) , 286-303. 303. doi:10.1002/mds.29288 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/82170

Title

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

Author(s)

Vollstedt E.J.

Author's Affiliation

Ramathibodi Hospital
 University of Health Sciences
 Juntendo University Graduate School of Medicine
 University of Dundee School of Medicine
 Department of Clinical Neurosciences
 Institutionen för Kliniska Vetenskaper, Lund
 The Michael J. Fox Foundation for Parkinson‘s Research
 Oslo Universitetssykehus
 Research Center of Neurology
 NorthShore University HealthSystem
 Donders Institute for Brain, Cognition and Behaviour
 Azienda Ospedaliero-Universitaria Sant'Andrea
 Hertie-Institut für klinische Hirnforschung
 National Taiwan University Hospital
 University of Luxembourg
 Instituto Nacional de Ciencias Neurologicas
 Universidad Peruana Cayetano Heredia
 Poznan University of Medical Sciences
 Medical University of Warsaw
 Université de Tunis El Manar, Institut National de Neurologie
 Hospital Universitario Virgen del Rocío
 Griffith University
 Pontificia Universidad Catolica Argentina
 Erasmus MC
 Universita degli Studi di Urbino Carlo Bo
 Pavol Jozef Safarik University in Kosice
 Columbia University
 North-West University
 Universiti Malaya
 National and Kapodistrian University of Athens
 Charité – Universitätsmedizin Berlin
 The University of Tokyo
 National Taiwan Normal University
 Indiana University School of Medicine
 Instituto de Medicina Molecular João Lobo Antunes
 Consiglio Nazionale delle Ricerche
 Santa Maria Hospital, Lisbon
 Chang Gung University
 Mater Misericordiae University Hospital
 Centro Hospitalar e Universitário de Coimbra
 Università degli Studi di Napoli Federico II
 Hospital Universitario Central de Asturias
 University of Toronto
 King Faisal Specialist Hospital and Research Centre
 Hôpital Universitaire Pitié Salpêtrière
 Università degli Studi di Pavia
 Universidade Federal de São Paulo
 Universitair Ziekenhuis Antwerpen
 Icahn School of Medicine at Mount Sinai
 Universität zu Lübeck
 Christian-Albrechts-Universität zu Kiel
 İstanbul Tıp Fakültesi
 Karolinska Institutet
 Vagelos College of Physicians and Surgeons
 Medizinische Universität Wien
 Juntendo University School of Medicine
 Hospital de La Santa Creu I Sant Pau
 Universidade de São Paulo
 Eginition Hospital
 Koç Üniversitesi
 Tel Aviv University
 Universidade do Estado do Rio de Janeiro
 Consejo Nacional de Investigaciones Científicas y Técnicas
 Faculty of Medicine and Health Sciences
 Baylor College of Medicine
 Albert Einstein College of Medicine of Yeshiva University
 Mayo Clinic in Jacksonville, Florida
 Universitat de Barcelona
 Sorbonne Université
 Division of Neurology

Other Contributor(s)

Mahidol University

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.

Keyword(s)

Neuroscience

Availability

URI

https://repository.li.mahidol.ac.th/handle/123456789/82170

Collections

Scopus 2023