Embracing Monogenic Parkinson's Disease: The MJFF Global Genetic PD Cohort.
Parkinson's disease
monogenic PD
Journal
Movement disorders : official journal of the Movement Disorder Society
ISSN: 1531-8257
Titre abrégé: Mov Disord
Pays: United States
ID NLM: 8610688
Informations de publication
Date de publication:
02 2023
02 2023
Historique:
revised:
20
07
2022
received:
22
04
2022
accepted:
27
07
2022
pubmed:
25
1
2023
medline:
25
2
2023
entrez:
24
1
2023
Statut:
ppublish
Résumé
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. 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. 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. 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. 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.
Sections du résumé
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.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
286-303Subventions
Organisme : Department of Health
ID : BRC-1215-20014
Pays : United Kingdom
Investigateurs
Anna Aasly
(A)
Jan O Aasly
(JO)
Natalya Y Abramycheva
(NY)
Azlina Ahmad-Annuar
(A)
Alberto Albanese
(A)
Roy N Alcalay
(RN)
Amaal Aldakheel
(A)
Thamer Alkhairallah
(T)
Bashayer Al-Mubarak
(B)
Nada Al-Tassan
(N)
Victoria Alvarez
(V)
Paolo Amami
(P)
Grazia Annesi
(G)
Silke Appel-Cresswell
(S)
Marco Antonio Araujo Leite
(MAA)
David Arkadir
(D)
Micol Avenali
(M)
Henrique Ballalai Ferraz
(HB)
Soraya Bardien
(S)
Melinda Barkhuizen
(M)
Matthew J Barrett
(MJ)
A Nazlı Başak
(AN)
Daniela Berg
(D)
Basar Bilgic
(B)
Bastiaan R Bloem
(BR)
Vincenzo Bonifati
(V)
Agnita J W Boon
(AJW)
Vanderci Borges
(V)
Friederike Borngräber
(F)
Max Borsche
(M)
Maria Bozi
(M)
Susan Bressman
(S)
Alexis Brice
(A)
Laura Brighina
(L)
Kathrin Brockmann
(K)
Norbert Brüggemann
(N)
Marta Camacho
(M)
Andrea Carmine Belin
(AC)
Jonathan Carr
(J)
Martin Emiliano Cesarini
(ME)
Mario Cornejo-Olivas
(M)
Bruce Chase
(B)
Sun Ju Chung
(SJ)
Leonor Correia Guedes
(LC)
Jordi Clarimon
(J)
Lorraine Clark
(L)
Jean-Christophe Corvol
(JC)
David Crosiers
(D)
Parimal Das
(P)
Patricia de Carvalho Aguiar
(P)
Joana Damásio
(J)
Giuseppe de Michele
(G)
Anna De Rosa
(A)
Elena Dieguez
(E)
Jolanta Dorszewska
(J)
Sibel Ertan
(S)
Stanley Fahn
(S)
Matthew J Farrer
(MJ)
Ekaterina Y Fedotova
(EY)
Rosangela Ferese
(R)
Joaquim J Ferreira
(JJ)
Tatiana Foroud
(T)
Manabu Funayama
(M)
Victor S C Fung
(VSC)
Monica Gagliardi
(M)
Stefano Gambardella
(S)
Gaetan Garraux
(G)
Alicia Garrido
(A)
Emilia M Gatto
(EM)
Gençer Genç
(G)
Nir Giladi
(N)
Pilar Gómez-Garre
(P)
Hasmet Hanagasi
(H)
Nobutaka Hattori
(N)
Faycel Hentati
(F)
Jens Michael Hertz
(JM)
Sergey N Illarioshkin
(SN)
Joseph Jankovic
(J)
Cristina Januario
(C)
Silvia Jesús Maestre
(SJ)
Valtteri Kaasinen
(V)
Meike Kasten
(M)
Hiroshi Kataoka
(H)
Anneke A Kievit
(AA)
Yun Joong Kim
(YJ)
Christine Klein
(C)
Péter Klivényi
(P)
Vladimir S Kostic
(VS)
Dariusz Koziorowski
(D)
Rejko Krüger
(R)
Andrea A Kühn
(AA)
Gregor Kuhlenbäumer
(G)
Ming-Che Kuo
(MC)
Anthony E Lang
(AE)
Guey-Jen Lee-Chen
(GJ)
Suzanne Lesage
(S)
Jia Lun Lim
(JL)
Shen-Yang Lim
(SY)
Chin-Hsien Lin
(CH)
Katja Lohmann
(K)
Timothy Lynch
(T)
Karen Marder
(K)
Katerina Markopoulou
(K)
Mika Martikainen
(M)
Patrick May
(P)
Allan McCarthy
(A)
George D Mellick
(GD)
Manuel Menéndez-González
(M)
Marcelo Merello
(M)
Pablo Mir
(P)
Anat Mirelman
(A)
Brit Mollenhauer
(B)
Hugo Morales Briceno
(HM)
Ana Morgadinho
(A)
Huw Morris
(H)
Alexandra Mosejova
(A)
Kenya Nishioka
(K)
Özgür Öztop Çakmak
(ÖÖ)
Diana A Olszewska
(DA)
Avi Orr-Urtreger
(A)
Sinthuja Pachchek
(S)
Shalini Padmanabhan
(S)
Maria Teresa Periñán
(MT)
Simona Petrucci
(S)
Marcia M G Pimentel
(MMG)
Radha Procopio
(R)
Teeratorn Pulkes
(T)
Andreas Puschmann
(A)
Caroline Ran
(C)
Olaf Riess
(O)
Owen A Ross
(OA)
Malco Rossi
(M)
Javier Ruiz-Martinez
(J)
Esther M Sammler
(EM)
João Santos Pereira
(JS)
Wataru Satake
(W)
Rachel Saunders-Pullman
(R)
Susen Schaake
(S)
Maria Skaalum Petersen
(MS)
Matej Skorvanek
(M)
Leonidas Stefanis
(L)
Alexandra I Soto-Beasley
(AI)
Mário Sousa
(M)
Mariana Spitz
(M)
Oksana Suchowersky
(O)
Carolyn M Sue
(CM)
Ai Huey Tan
(AH)
Eng-King Tan
(EK)
Avner Thaler
(A)
Fatih Tepgeç
(F)
Pichet Termsarasab
(P)
Christelle Tesson
(C)
Tatsushi Toda
(T)
Mathias Toft
(M)
Eduardo Tolosa
(E)
Luis Torres-Ramirez
(L)
Vitor Tumas
(V)
Oya Uyguner
(O)
Enza Maria Valente
(EM)
Bart van de Warrenburg
(B)
Marie Vidailhet
(M)
Eva-Juliane Vollstedt
(EJ)
Ronald L Walton
(RL)
Cheryl Waters
(C)
Caroline H Williams-Gray
(CH)
Juliane Winkelmann
(J)
Yih-Ru Wu
(YR)
Isabel Wurster
(I)
Zbigniew K Wszolek
(ZK)
Ruey-Meei Wu
(RM)
Bao-Rong Zhang
(BR)
Alexander Zimprich
(A)
Informations de copyright
© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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