guest ::
| Home > Articles > Published articles > Embracing Monogenic Parkinson's Disease : |
| Home > Articles > Published articles > Embracing Monogenic Parkinson's Disease : |
(Institute of Neurogenetics. University of Lübeck (Alemanya)) (Institute of Neurogenetics. University of Lübeck (Alemanya)) (Sorbonne University. Paris Brain Institute (França)) (Neurological Institute. Tel-Aviv Medical Center (Tel-Aviv, Israel)) (Psychotherapy and Institute of Neurogenetics. University of Lübeck (Alemanya)) (University of Lübeck. Department of Neurology and Institute of Neurogenetics (Alemanya)) (Institut d'Investigacions Biomèdiques August Pi i Sunyer) (Instituto de Medicina Molecular João Lobo Antunes. University of Lisbon (Portugal)) (Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias) (Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias) (Instituto de Biomedicina de Sevilla) (Instituto de Biomedicina de Sevilla) (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (Madrid)) (Taiwan University Hospital (Taipei, Taiwan)) (Mayo Clinic Florida (Jacksonville, Estats Units d'Amèrica)) (Mayo Clinic Florida (Jacksonville, Estats Units d'Amèrica)) (Juntendo University School of Medicine (Bunkyo, Japó)) (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya)) (University of Cambridge (Regne Unit)) (University of Cambridge (Regne Unit)) (Instituto Nacional de Ciencias Neurologicas (Lima, Perú)) (Ramathibodi Hospital. Mahidol University (Bangkok, Tailàndia)) (Charité-Universitätsmedizin Berlin) (Charité-Universitätsmedizin Berlin) (Medical University Vienna (Àustria)) (IRCCS Neuromed. University of Urbino (Itàlia)) (University HealthSystem Evanston (Estats Units d'Amèrica)) (Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET)) (The Dublin Neurological Institute at the Mater Misericordiae University Hospital (Irlanda)) (University of Malaya (Kuala Lumpur, Malàsia)) (DST/NWU Preclinical Drug Development Platform. North-West University (Potchefstroom, Sud-àfrica)) (Oslo University Hospital (Oslo, Noruega)) (The University of British Columbia (Canadà)) (Parkinson Research Clinic. Centre Hospitalier de Luxembourg) (Ninewells Hospital and Medical School (Dundee, Regne Unit)) (Second Affiliated Hospital. Zhejiang University School of Medicine (Hangzhou, Xina)) (Asan Medical Center (Seül, Corea del Sud)) (Singapore General Hospital (Singapur)) (University Medical Center Göttingen (Alemanya)) (The Faroese Hospital System & University of the Faroe Islands (Tórshavn, Illes Fèroe)) (University of Pavia (Itàlia)) (University of Florida (Gainesville, estats Units d'Amèrica)) (University of Tübingen and DZNE (Tübingen, Alemanya)) (Westmead Hospital) (Ministry of Science and Higher Education (Rússia)) (Universitário de Coimbra (Portugal)) (Institute of Neurogenetics. University of Lübeck (Lübeck, Alemanya)) (UCL Queen Square Institute of Neurology (Londres, Regne Unit)) (Pedro Ernesto University Hospital, State University of Rio de Janeiro (Brasil)) (Universitário de Coimbra (Portugal)) (National Taiwan University Hospital (Taipei, Taiwan))| Date: | 2023 |
| Abstract: | 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. 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. 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. |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Parkinson's disease ; Monogenic PD |
| Published in: | Movement Disorders, Vol. 38 Núm. 2 (01 2023) , p. 286-303, ISSN 1531-8257 |
