Parkinson's Disease Gene Screening in Familial Cases from Central and South America
Author(s)
Seysha Mehta
Janvi Ramchandra
Sekinat Mumuney
Artur Francisco Schumacher Schuh
Mario Cornejo‐Olivas
Elison Sarapura‐Castro
Luis Torres
Miguel Inca‐Martinez
Pilar Mazzetti
Carlos Cosentino
Federico Micheli
Vítor Tumas
Elena Diéguez
Víctor Raggio
Vanderci Borges
Henrique Ballalai Ferraz
Pedro Chaná‐Cuevas
Marlene Jiménez-Del-Río
Carlos Velez‐Pardo
Sonia Moreno
Francisco Lopera
Jorge Luis Orozco-Velez
Beatriz Muñoz
Carlos Roberto de Mello Rieder
Alex Medina‐Escobar
Dora Yearout
Cyrus P. Zabetian
Ignácio F. Mata
Date Issued
25 de julio de 2024
Type
Article
Volume
39
Issue
10
Start Page
1843
End Page
1855
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.
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