Parkinson's Disease Gene Screening in Familial Cases from Central and South America
Resumen:
Background: Parkinson's disease (PD) is the second most common neurodegenerative disease following Alzheimer's disease. Nearly 30 causative genes have been identified for PD and related disorders. However, most of these genes were identified in European-derived families, and little is known about their role in Latin American populations. Objectives: Our goal was to assess the spectrum and frequency of pathogenic variants in known PD genes in familial PD patients from Latin America. Methods: We selected 335 PD patients with a family history of PD from the Latin American Research Consortium on the Genetics of PD. We capture-sequenced the coding regions of 26 genes related to neurodegenerative parkinsonism. Of the 335 PD patients, 324 had sufficient sequencing coverage to be analyzed. Results: We identified pathogenic variants in 41 individuals (12.7%) in FBXO7, GCH1, LRRK2, PARK7, PINK1, PLA2G6, PRKN, SNCA, and TARDBP, GBA1 risk variants in 25 individuals (7.7%), and variants of uncertain significance in another 24 individuals (7.4%) in ATP13A2, ATP1A3, DNAJC13, DNAJC6, GBA1, LRKK2, PINK1, VPS13C, and VPS35. Of the 70 unique variants identified, 19 were more frequent in Latin Americans than in any other population. Conclusions: This is the first screening of known PD genes in a large cohort of patients with familial PD from Latin America. There were substantial differences in the spectrum of variants observed in comparison to previous findings from PD families of European origin. Our data provide further evidence that differences exist between the genetic architecture of PD in Latinos and European-derived populations. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
| 2024 | |
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Parkinson's disease Genetics Hispanic Latino Pathogenic variant ENFERMEDAD DE PARKINSON ADULTO ANCIANO PERSONA DE MEDIANA EDAD GENÉTICA PREDISPOSICIÓN GENÉTICA A LA ENFERMEDAD MÉTODOS PRUEBAS GENÉTICAS |
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| Inglés | |
| Universidad de la República | |
| COLIBRI | |
| https://hdl.handle.net/20.500.12008/56379 | |
| Acceso abierto | |
| Licencia Creative Commons Atribución - No Comercial - Sin Derivadas (CC - By-NC-ND 4.0) |
| Sumario: | Oswaldo Lorenzo-Betancor 1 2, Seysha Mehta 3, Janvi Ramchandra 4 5, Sekinat Mumuney 3, Artur F Schumacher-Schuh 6 7, Mario Cornejo-Olivas 8 9, Elison H Sarapura-Castro 8 9, Luis Torres 10, Miguel A Inca-Martinez 4, Pilar Mazzetti 9 11, Carlos Cosentino 10 11, Federico Micheli 12 13, Vitor Tumas 14, Elena Dieguez 15, Victor Raggio 16, Vanderci Borges 17, Henrique B Ferraz 17, Pedro Chana-Cuevas 18, Marlene Jimenez-Del-Rio 19, Carlos Velez-Pardo 19, Sonia Moreno 19, Francisco Lopera 19, Jorge L Orozco-Velez 20 21, Beatriz Muñoz-Ospina 20 21, Carlos R M Rieder 22, Alex Medina-Escobar 23 24, Dora Yearout 1 2, Cyrus P Zabetian 1 2, Ignacio F Mata 1 2 3 4; Latin American Research Consortium on the Genetics of PD (LARGE‐PD) |
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