Embracing Monogenic Parkinson's Disease: The <scp>MJFF</scp> Global Genetic <scp>PD</scp> Cohort
Author(s)
Susen Schaake
Katja Lohmann
Shalini Padmanabhan
Alexis Brice
Suzanne Lesage
Christelle Tesson
Marie Vidailhet
Isabel Wurster
F. Hentati
Anat Mirelman
Nir Giladi
Karen Marder
Cheryl Waters
Stanley Fahn
Meike Kasten
Norbert Brüggemann
Max Borsche
Tatiana Foroud
Eduardo Tolosa
Alícia Garrido
Grazia Annesi
Monica Gagliardi
Maria Bozi
Leonidas Stefanis
Joaquim J. Ferreira
Leonor Correia Guedes
Micol Avenali
Simona Petrucci
Lorraine N. Clark
E. Yu. Fedotova
Natalya Abramycheva
Victoria Álvarez
Manuel Menéndez‐González
S. Jesús Maestre
Pilar Gómez‐Garre
Pablo Mir
Andrea Carmine Belin
Caroline Ran
Chin‐Hsien Lin
Ming‐Che Kuo
David Crosiers
Zbigniew K. Wszołek
Owen A. Ross
Joseph Jankovic
Kenya Nishioka
Manabu Funayama
Jordi Clarimón
Caroline H. Williams‐Gray
Marta Camacho
Mario Cornejo‐Olivas
Luis Torres-Ramírez
Yih‐Ru Wu
Guey‐Jen Lee‐Chen
Ana Morgadinho
Teeratorn Pulkes
Pichet Termsarasab
Daniela Berg
Gregor Kuhlenbäumer
Andrea A. Kühn
Friederike Borngräber
Giuseppe De Michele
Anna De Rosa
Alexander Zimprich
Andreas Puschmann
George D. Mellick
Jolanta Dorszewska
Jonathan Carr
Rosangela Ferese
Stefano Gambardella
Bruce A. Chase
Katerina Markopoulou
Wataru Satake
Tatsushi Toda
Malco Rossi
Marcelo Merello
Timothy Lynch
Diana A. Olszewska
Shen‐Yang Lim
Azlina Ahmad‐Annuar
Ai Huey Tan
Bashayer Al‐Mubarak
Haşmet Hanağası
Dariusz Koziorowski
Sibel Ertan
Gençer Genç
Patrícia de Carvalho Aguiar
Melinda Barkhuizen
Márcia Mattos Gonçalves Pimentel
Rachel Saunders‐Pullman
Bart van de Warrenburg
Susan Bressman
Mathias Toft
Silke Appel‐Cresswell
Anthony E. Lang
Matěj Škorvánek
Agnita J.W. Boon
Rejko Krüger
Esther Sammler
Vítor Tumas
Baorong Zhang
Gaëtan Garraux
Sun Ju Chung
Yun Joong Kim
Juliane Winkelmann
Carolyn M. Sue
Eng‐King Tan
Joana Damásio
Péter Klivènyi
Vladimir Kostić
David Arkadir
Mika H. Martikainen
Vanderci Borges
Jens Michael Hertz
Laura Brighina
Mariana Spitz
Oksana Suchowersky
Olaf Rieß
Parimal Das
Brit Mollenhauer
Emilia Gatto
Maria Skaalum Petersen
Nobutaka Hattori
Ruey‐Meei Wu
С. Н. Иллариошкин
Enza Maria Valente
Jan Aasly
Anna Aasly
Roy N. Alcalay
Avner Thaler
Matthew J. Farrer
Kathrin Brockmann
Jean‐Christophe Corvol
Christine Klein
the MJFF Global Genetic Parkinson's Disease Study Group
Date Issued
24 de enero de 2023
Type
Article
Volume
38
Issue
2
Start Page
286
End Page
303
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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