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Parkinson's Disease Gene Screening in Familial Cases from Central and South America
Author(s)
University of Washington
Seysha Mehta
Cleveland Clinic Lerner College of Medicine
Janvi Ramchandra
Cleveland Clinic
Sekinat Mumuney
Cleveland Clinic Lerner College of Medicine
Artur Francisco Schumacher Schuh
Universidade Federal do Rio Grande do Sul
Mario Cornejo‐Olivas
Universidad Científica del Sur
Elison Sarapura‐Castro
Universidad Científica del Sur
Luis Torres
Instituto Nacional de Ciencias Neurológicas
Miguel Inca‐Martinez
Cleveland Clinic
Pilar Mazzetti
National University of San Marcos
Carlos Cosentino
National University of San Marcos
Federico Micheli
Universidad de Buenos Aires
Vítor Tumas
Universidade de São Paulo
Elena Diéguez
Universidad de la República de Uruguay
Víctor Raggio
Universidad de la República de Uruguay
Vanderci Borges
Universidade Federal de São Paulo
Henrique Ballalai Ferraz
Universidade Federal de São Paulo
Pedro Chaná‐Cuevas
Universidad de Santiago de Chile
Marlene Jiménez-Del-Río
Universidad de Antioquia
Carlos Velez‐Pardo
Universidad de Antioquia
Sonia Moreno
Universidad de Antioquia
Francisco Lopera
Universidad de Antioquia
Jorge Luis Orozco-Velez
Fundación Valle del Lili
Beatriz Muñoz
Fundación Valle del Lili
Carlos Roberto de Mello Rieder
Universidade Federal de Ciências da Saúde de Porto Alegre
Alex Medina‐Escobar
National Autonomous University of Honduras
Dora Yearout
University of Washington
Cyrus P. Zabetian
University of Washington
Ignácio F. Mata
Cleveland Clinic
Date Issued
25 de julio de 2024
Type
Article
Volume
39
Issue
10
Series/Report No.
Movement Disorders
Start Page
1843
End Page
1855
ISSN
0885-3185
1531-8257
Abstract
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.
Keywords