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. 2024 Oct;39(10):1843-1855.
doi: 10.1002/mds.29931. Epub 2024 Jul 25.

Parkinson's Disease Gene Screening in Familial Cases from Central and South America

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)
Collaborators, Affiliations

Parkinson's Disease Gene Screening in Familial Cases from Central and South America

Oswaldo Lorenzo-Betancor et al. Mov Disord. 2024 Oct.

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: Hispanic; Latino; Parkinson's disease; genetics; pathogenic variant.

PubMed Disclaimer

Conflict of interest statement

Recruitment of LARGE-PD participants was originally funded by an International Research Program Grant (2010-2012) to C.P.Z. and I.F.M and by a Stanley Fahn Junior Faculty Award (2016-2019) to I.F.M., both from the Parkinson’s Disease Foundation. This work was funded by a research grant from the American Parkinson’s Disease Association to I.F.M. and with resources and the use of facilities at the Veterans Affairs Puget Sound Health Care System (O.L.B, D.Y., C.P.Z., and I.F.M.).

I.F.M. also receives funding from the National Institutes of Health (NIH) grant R01 1R01NS112499-01A1, the Michael J. Fox Foundation, and the Aligning Science Across Parkinson’s initiative. M.C.-O. and E.H.S.-C. were supported by the D43TW009345 Global Health Research Fellowship.

Figures

Figure 1.
Figure 1.
A. Sample distribution across countries. B. Pathogenic variants and variants of uncertain significance carriers’ distribution by gene. C. Pathogenic variants and variants of uncertain significance distribution by gene. VUS = Variant of uncertain significance. *Pathogenic GBA1 counts refer to individuals carrying variants that cause GD and/or are considered risk factors for PD.
Figure 2.
Figure 2.. Distribution of pathogenic variants and variants of uncertain significance by countries.
A. Pathogenic variants. *Pathogenic GBA1 counts refer to individuals carrying variants that cause GD and/or are considered risk factors for PD. B. Variants of uncertain significance.
Figure 3.
Figure 3.. Copy number variants examples identified using the panelcn.MOPS package.
The normalized RCs of each test sample and all controls are displayed as boxplots for each exon. Exons are displayed in chromosomal order for each gene. The RCs of each control sample are symbolized by black dots, whereas the RCs of the test sample are highlighted by red dots. A deviation of the test sample over the boxplot and whiskers represents a duplication, while its deviation below the boxplot and whiskers, represents a deletion. Depending on the degree of deviation the duplication or deletion can be either heterozygous or homozygous. A. PARK7 Ex3 and Ex5 compound heterozygous duplication; B. PRKN Ex1-Ex4 homozygous duplication; C. PRKN Ex5 heterozygous deletion and Ex6 homozygous deletion; D. Entire SNCA heterozygous duplication; E. SNCA Ex1 heterozygous duplication; F. SNCA Ex2 heterozygous deletion.
See this image and copyright information in PMC

References

    1. Poewe W, Seppi K, Tanner CM, et al. Parkinson disease. Nat Rev Dis Primers 2017;3:17013. - PubMed
    1. de Rijk MC, Launer LJ, Berger K, et al. Prevalence of Parkinson’s disease in Europe: A collaborative study of population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology 2000;54(11 Suppl 5):S21–23. - PubMed
    1. Van Den Eeden SK, Tanner CM, Bernstein AL, et al. Incidence of Parkinson’s disease: variation by age, gender, and race/ethnicity. Am J Epidemiol 2003;157(11):1015–1022. - PubMed
    1. Blauwendraat C, Nalls MA, Singleton AB. The genetic architecture of Parkinson’s disease. Lancet Neurol 2020;19(2):170–178. - PMC - PubMed
    1. Cormand B, Montfort M, Chabas A, Vilageliu L, Grinberg D. Genetic fine localization of the beta-glucocerebrosidase (GBA) and prosaposin (PSAP) genes: implications for Gaucher disease. Hum Genet 1997;100(1):75–79. - PubMed