TY - JOUR
T1 - Embracing Monogenic Parkinson's Disease
T2 - The MJFF Global Genetic PD Cohort
AU - the MJFF Global Genetic Parkinson's Disease Study Group
AU - Vollstedt, Eva Juliane
AU - Schaake, Susen
AU - Lohmann, Katja
AU - Padmanabhan, Shalini
AU - Brice, Alexis
AU - Lesage, Suzanne
AU - Tesson, Christelle
AU - Vidailhet, Marie
AU - Wurster, Isabel
AU - Hentati, Faycel
AU - Mirelman, Anat
AU - Giladi, Nir
AU - Marder, Karen
AU - Waters, Cheryl
AU - Fahn, Stanley
AU - Kasten, Meike
AU - Brüggemann, Norbert
AU - Borsche, Max
AU - Foroud, Tatiana
AU - Tolosa, Eduardo
AU - Garrido, Alicia
AU - Annesi, Grazia
AU - Gagliardi, Monica
AU - Bozi, Maria
AU - Stefanis, Leonidas
AU - Ferreira, Joaquim J.
AU - Correia Guedes, Leonor
AU - Avenali, Micol
AU - Petrucci, Simona
AU - Clark, Lorraine
AU - Fedotova, Ekaterina Y.
AU - Abramycheva, Natalya Y.
AU - Alvarez, Victoria
AU - Menéndez-González, Manuel
AU - Jesús Maestre, Silvia
AU - Gómez-Garre, Pilar
AU - Mir, Pablo
AU - Belin, Andrea Carmine
AU - Ran, Caroline
AU - Lin, Chin Hsien
AU - Kuo, Ming Che
AU - Crosiers, David
AU - Wszolek, Zbigniew K.
AU - Ross, Owen A.
AU - Jankovic, Joseph
AU - Nishioka, Kenya
AU - Funayama, Manabu
AU - Clarimon, Jordi
AU - Williams-Gray, Caroline H.
AU - Winkelmann, Juliane
N1 - Publisher Copyright:
© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
PY - 2023/2/1
Y1 - 2023/2/1
N2 - 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.
AB - 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.
KW - Parkinson's disease
KW - monogenic PD
UR - https://www.scopus.com/pages/publications/85147202939
U2 - 10.1002/mds.29288
DO - 10.1002/mds.29288
M3 - Article
C2 - 36692014
AN - SCOPUS:85147202939
SN - 0885-3185
VL - 38
SP - 286
EP - 303
JO - Movement Disorders
JF - Movement Disorders
IS - 2
ER -