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

Lorenzo-Betancor, Oswaldo - Mehta, Seysha - Ramchandra, Janvi - Dieguez, Eliana - Raggio, Víctor

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.

Detalles Bibliográficos
2024
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
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)
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author Lorenzo-Betancor, Oswaldo
author2 Mehta, Seysha
Ramchandra, Janvi
Dieguez, Eliana
Raggio, Víctor
author2_role author
author
author
author
author_facet Lorenzo-Betancor, Oswaldo
Mehta, Seysha
Ramchandra, Janvi
Dieguez, Eliana
Raggio, Víctor
author_role author
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dc.contributor.filiacion.none.fl_str_mv Lorenzo-Betancor Oswaldo, University of Washington (E.E.U.U.). School of Medicine. Department of Neurology; Veterans Affairs Puget Sound Health Care System (E.E.U.U.)
Mehta Seysha, Case Western Reserve University (E.E.U.U.). Cleveland Clinic Lerner College of Medicine
Ramchandra Janvi, Cleveland Clinic Foundation Lerner Research Institute (E.E.U.U.). Genomic Medicine Institute; Case Western Reserve University (E.E.U.U.). Department of Biochemistry
Dieguez Eliana, Universidad de la República (Uruguay). Facultad de Medicina. Hospital de Clínicas. Instituto de Neurología
Raggio Víctor, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de Genética
dc.coverage.spatial.es.fl_str_mv SUDAMÉRICA
CENTROAMÉRICA
dc.creator.none.fl_str_mv Lorenzo-Betancor, Oswaldo
Mehta, Seysha
Ramchandra, Janvi
Dieguez, Eliana
Raggio, Víctor
dc.date.accessioned.none.fl_str_mv 2026-08-17T15:04:12Z
dc.date.available.none.fl_str_mv 2026-08-17T15:04:12Z
dc.date.issued.none.fl_str_mv 2024
dc.description.abstract.none.fl_txt_mv 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.
dc.description.es.fl_txt_mv 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)
Affiliations 1Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA. 2Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA. 3Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. 4Genomic Medicine Institute, Cleveland Clinic Foundation Lerner Research Institute, Cleveland, Ohio, USA. 5Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA. 6Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 7Department of Neurology, Clinics Hospital of Porto Alegre, Porto Alegre, Brazil. 8Neurogenetics Working Group, Universidad Científica del Sur, Lima, Peru. 9Neurogenetics Research Center, National Institute of Neurological Sciences, Lima, Peru. 10Movement Disorders Unit, National Institute of Neurological Sciences, Lima, Peru. 11School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru. 12Parkinson's Disease and Movement Disorders Center, University of Buenos Aires, Buenos Aires, Argentina. 13Centro de Parkinson y Movimientos Anormales, Fundación San Gabriel, Córdoba, Argentina. 14Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil. 15Neurology Institute, Universidad de la Republica, Montevideo, Uruguay. 16Department of Genetics, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay. 17Movement Disorders Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, Brazil. 18Centro de Trastornos del Movimiento (CETRAM), Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Santiago de Chile, Chile. 19Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, Universidad de Antioquia, Medellín, Colombia. 20Department of Neurology, Valle del Lili Foundation, Cali, Colombia. 21Department of Human Sciences, Icesi University, Cali, Colombia. 22Departamento de Neurologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil. 23Department of Neurology, Universidad Nacional Autónoma de Honduras, Tegucigalpa, Honduras. 24The Moncton City Hospital, Moncton, New Brunswick, Canada.
dc.format.extent.es.fl_str_mv 13 p.
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dc.identifier.citation.es.fl_str_mv Lorenzo-Betancor O, Mehta S, Ramchandra J y otros. Parkinson's Disease Gene Screening in Familial Cases from Central and South America. Movement Disorders [en línea]. 2024;39(10):1843-1855
dc.identifier.doi.none.fl_str_mv 10.1002/mds.29931
dc.identifier.eissn.none.fl_str_mv 1531-8257
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/20.500.12008/56379
dc.language.iso.none.fl_str_mv en
eng
dc.publisher.es.fl_str_mv Raven Press
dc.relation.none.fl_str_mv Movement Disorders, 2024;39(10):1843-1855
dc.rights.license.none.fl_str_mv Licencia Creative Commons Atribución - No Comercial - Sin Derivadas (CC - By-NC-ND 4.0)
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
dc.source.none.fl_str_mv reponame:COLIBRI
instname:Universidad de la República
instacron:Universidad de la República
dc.subject.es.fl_str_mv Parkinson's disease
Genetics
Hispanic
Latino
Pathogenic variant
dc.subject.other.es.fl_str_mv ENFERMEDAD DE PARKINSON
ADULTO
ANCIANO
PERSONA DE MEDIANA EDAD
GENÉTICA
PREDISPOSICIÓN GENÉTICA A LA ENFERMEDAD
MÉTODOS
PRUEBAS GENÉTICAS
dc.title.none.fl_str_mv Parkinson's Disease Gene Screening in Familial Cases from Central and South America
dc.type.es.fl_str_mv Artículo
dc.type.none.fl_str_mv info:eu-repo/semantics/article
dc.type.version.none.fl_str_mv info:eu-repo/semantics/publishedVersion
description 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)
eu_rights_str_mv openAccess
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identifier_str_mv Lorenzo-Betancor O, Mehta S, Ramchandra J y otros. Parkinson's Disease Gene Screening in Familial Cases from Central and South America. Movement Disorders [en línea]. 2024;39(10):1843-1855
10.1002/mds.29931
1531-8257
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publishDate 2024
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repository.mail.fl_str_mv karina.camps@seciu.edu.uy
repository.name.fl_str_mv COLIBRI - Universidad de la República
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rights_invalid_str_mv Licencia Creative Commons Atribución - No Comercial - Sin Derivadas (CC - By-NC-ND 4.0)
spelling Lorenzo-Betancor Oswaldo, University of Washington (E.E.U.U.). School of Medicine. Department of Neurology; Veterans Affairs Puget Sound Health Care System (E.E.U.U.)Mehta Seysha, Case Western Reserve University (E.E.U.U.). Cleveland Clinic Lerner College of MedicineRamchandra Janvi, Cleveland Clinic Foundation Lerner Research Institute (E.E.U.U.). Genomic Medicine Institute; Case Western Reserve University (E.E.U.U.). Department of BiochemistryDieguez Eliana, Universidad de la República (Uruguay). Facultad de Medicina. Hospital de Clínicas. Instituto de NeurologíaRaggio Víctor, Universidad de la República (Uruguay). Facultad de Medicina. Departamento de GenéticaSUDAMÉRICACENTROAMÉRICA2026-08-17T15:04:12Z2026-08-17T15:04:12Z2024Lorenzo-Betancor O, Mehta S, Ramchandra J y otros. Parkinson's Disease Gene Screening in Familial Cases from Central and South America. Movement Disorders [en línea]. 2024;39(10):1843-1855https://hdl.handle.net/20.500.12008/5637910.1002/mds.299311531-8257Oswaldo 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)Affiliations 1Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA. 2Department of Neurology, University of Washington School of Medicine, Seattle, Washington, USA. 3Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA. 4Genomic Medicine Institute, Cleveland Clinic Foundation Lerner Research Institute, Cleveland, Ohio, USA. 5Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA. 6Department of Pharmacology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. 7Department of Neurology, Clinics Hospital of Porto Alegre, Porto Alegre, Brazil. 8Neurogenetics Working Group, Universidad Científica del Sur, Lima, Peru. 9Neurogenetics Research Center, National Institute of Neurological Sciences, Lima, Peru. 10Movement Disorders Unit, National Institute of Neurological Sciences, Lima, Peru. 11School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru. 12Parkinson's Disease and Movement Disorders Center, University of Buenos Aires, Buenos Aires, Argentina. 13Centro de Parkinson y Movimientos Anormales, Fundación San Gabriel, Córdoba, Argentina. 14Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil. 15Neurology Institute, Universidad de la Republica, Montevideo, Uruguay. 16Department of Genetics, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay. 17Movement Disorders Unit, Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, São Paulo, Brazil. 18Centro de Trastornos del Movimiento (CETRAM), Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Santiago de Chile, Chile. 19Neuroscience Research Group, Medical Research Institute, Faculty of Medicine, Universidad de Antioquia, Medellín, Colombia. 20Department of Neurology, Valle del Lili Foundation, Cali, Colombia. 21Department of Human Sciences, Icesi University, Cali, Colombia. 22Departamento de Neurologia, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brazil. 23Department of Neurology, Universidad Nacional Autónoma de Honduras, Tegucigalpa, Honduras. 24The Moncton City Hospital, Moncton, New Brunswick, Canada.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.Submitted by Almiñana María Cecilia (marialminana@gmail.com) on 2026-08-14T19:01:57Z No. of bitstreams: 2 license_rdf: 27293 bytes, checksum: d62648cf14c1e37917d392ac87012955 (MD5) Parkinson's Disease Gene Screening.pdf: 9424091 bytes, checksum: 663d9998a8d0501a28e57f51235296f9 (MD5)Approved for entry into archive by Almiñana María Cecilia (marialminana@gmail.com) on 2026-08-17T14:10:09Z (GMT) No. of bitstreams: 2 license_rdf: 27293 bytes, checksum: d62648cf14c1e37917d392ac87012955 (MD5) Parkinson's Disease Gene Screening.pdf: 9424091 bytes, checksum: 663d9998a8d0501a28e57f51235296f9 (MD5)Made available in DSpace by Luna Fabiana (fabiana.luna@seciu.edu.uy) on 2026-08-17T15:04:12Z (GMT). No. of bitstreams: 2 license_rdf: 27293 bytes, checksum: d62648cf14c1e37917d392ac87012955 (MD5) Parkinson's Disease Gene Screening.pdf: 9424091 bytes, checksum: 663d9998a8d0501a28e57f51235296f9 (MD5) Previous issue date: 202413 p.application/pdfenengRaven PressMovement Disorders, 2024;39(10):1843-1855Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014)info:eu-repo/semantics/openAccessLicencia Creative Commons Atribución - No Comercial - Sin Derivadas (CC - By-NC-ND 4.0)Parkinson's diseaseGeneticsHispanicLatinoPathogenic variantENFERMEDAD DE PARKINSONADULTOANCIANOPERSONA DE MEDIANA EDADGENÉTICAPREDISPOSICIÓN GENÉTICA A LA ENFERMEDADMÉTODOSPRUEBAS GENÉTICASParkinson's Disease Gene Screening in Familial Cases from Central and South AmericaArtículoinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionreponame:COLIBRIinstname:Universidad de la Repúblicainstacron:Universidad de la RepúblicaLorenzo-Betancor, OswaldoMehta, SeyshaRamchandra, JanviDieguez, ElianaRaggio, VíctorLICENSElicense.txtlicense.txttext/plain; charset=utf-84267http://localhost:8080/xmlui/bitstream/20.500.12008/56379/5/license.txt6429389a7df7277b72b7924fdc7d47a9MD55CC-LICENSElicense_urllicense_urltext/plain; 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- Universidad de la Repúblicafalse
spellingShingle Parkinson's Disease Gene Screening in Familial Cases from Central and South America
Lorenzo-Betancor, Oswaldo
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
status_str publishedVersion
title Parkinson's Disease Gene Screening in Familial Cases from Central and South America
title_full Parkinson's Disease Gene Screening in Familial Cases from Central and South America
title_fullStr Parkinson's Disease Gene Screening in Familial Cases from Central and South America
title_full_unstemmed Parkinson's Disease Gene Screening in Familial Cases from Central and South America
title_short Parkinson's Disease Gene Screening in Familial Cases from Central and South America
title_sort Parkinson's Disease Gene Screening in Familial Cases from Central and South America
topic 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
url https://hdl.handle.net/20.500.12008/56379