Challenges in Clinico-Genetic Correlations in Parkinson’s disease (PD): The Role of Copy Number Variants (CNV)

Autores
Gatto, Emilia Mabel; Radrizzani Helguera, Martin; González Rojas, Natalia; Cesarini, Martin Emiliano; Etcheverry, José Luis; Perandones, Claudia
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Parkinson’s disease (PD) represents the second most common neurodegenerative disease and remains incurable. Mutations in multiple genes have been linked to monogenic PD (gPD); these monogenic forms, however, represent a small number of cases while in most instances PD appears as idiopathic (iPD). These findings raise the question of whether genetic and idiopathic parkinsonisms constitute the same disease. Nevertheless, monogenic-PD phenotypes and iPD both fulfill MDS criteria for PD, and show evidence of alpha-synuclein aggregates in both conditions. Distinct genetic loci in rare Mendelian forms have been identified as causal mutations, others as possible disease-causing genes, and genome-wide association studies have reported several risk loci, many of them located in the genes associated with the dominant mutations. Not only single-nucleotide polymorphisms (SNPs), but other kinds of DNA molecular defects as well have been spotted as significant disease-causing mutations, including large chromosomal structural rearrangements and copy number variations (CNVs). As their size varies, and detection methodologies have different sensitivity and resolution, CNVs pose a special challenge in genetic studies, and there currently is a debate on the pathogenetic or susceptibility impact of specific CNVs on PD. In this review, through multiple instances of experimental evidence, we analyze the impact on histopathology of the different mutational mechanisms involved in the genesis and etiology of PD. We believe that increasing our knowledge about the changes and implications at tissue level produced by each of those mechanisms will allow to develop much more suitable and personalized potential therapeutic strategies, biomarker identification, as well as disease modeling, agreeing with the precision medicine concept.
Fil: Gatto, Emilia Mabel. Instituto de Neurociencias Buenos Aires S. A.; Argentina
Fil: Radrizzani Helguera, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín; Argentina
Fil: González Rojas, Natalia. Instituto de Neurociencias Buenos Aires S. A.; Argentina
Fil: Cesarini, Martin Emiliano. Instituto de Neurociencias Buenos Aires S. A.; Argentina
Fil: Etcheverry, José Luis. Instituto de Neurociencias Buenos Aires S. A.; Argentina
Fil: Perandones, Claudia. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina
Materia
Parkinson Disease
Genetic Mosaicism.
Fluorescense-In-Situ-Hibridization
Copy Number Variant
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/149510

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network_name_str CONICET Digital (CONICET)
spelling Challenges in Clinico-Genetic Correlations in Parkinson’s disease (PD): The Role of Copy Number Variants (CNV)Gatto, Emilia MabelRadrizzani Helguera, MartinGonzález Rojas, NataliaCesarini, Martin EmilianoEtcheverry, José LuisPerandones, ClaudiaParkinson DiseaseGenetic Mosaicism.Fluorescense-In-Situ-HibridizationCopy Number Varianthttps://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Parkinson’s disease (PD) represents the second most common neurodegenerative disease and remains incurable. Mutations in multiple genes have been linked to monogenic PD (gPD); these monogenic forms, however, represent a small number of cases while in most instances PD appears as idiopathic (iPD). These findings raise the question of whether genetic and idiopathic parkinsonisms constitute the same disease. Nevertheless, monogenic-PD phenotypes and iPD both fulfill MDS criteria for PD, and show evidence of alpha-synuclein aggregates in both conditions. Distinct genetic loci in rare Mendelian forms have been identified as causal mutations, others as possible disease-causing genes, and genome-wide association studies have reported several risk loci, many of them located in the genes associated with the dominant mutations. Not only single-nucleotide polymorphisms (SNPs), but other kinds of DNA molecular defects as well have been spotted as significant disease-causing mutations, including large chromosomal structural rearrangements and copy number variations (CNVs). As their size varies, and detection methodologies have different sensitivity and resolution, CNVs pose a special challenge in genetic studies, and there currently is a debate on the pathogenetic or susceptibility impact of specific CNVs on PD. In this review, through multiple instances of experimental evidence, we analyze the impact on histopathology of the different mutational mechanisms involved in the genesis and etiology of PD. We believe that increasing our knowledge about the changes and implications at tissue level produced by each of those mechanisms will allow to develop much more suitable and personalized potential therapeutic strategies, biomarker identification, as well as disease modeling, agreeing with the precision medicine concept.Fil: Gatto, Emilia Mabel. Instituto de Neurociencias Buenos Aires S. A.; ArgentinaFil: Radrizzani Helguera, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín; ArgentinaFil: González Rojas, Natalia. Instituto de Neurociencias Buenos Aires S. A.; ArgentinaFil: Cesarini, Martin Emiliano. Instituto de Neurociencias Buenos Aires S. A.; ArgentinaFil: Etcheverry, José Luis. Instituto de Neurociencias Buenos Aires S. A.; ArgentinaFil: Perandones, Claudia. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaSciVision Publishers2021-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/149510Gatto, Emilia Mabel; Radrizzani Helguera, Martin; González Rojas, Natalia; Cesarini, Martin Emiliano; Etcheverry, José Luis; et al.; Challenges in Clinico-Genetic Correlations in Parkinson’s disease (PD): The Role of Copy Number Variants (CNV); SciVision Publishers; Genetics & Molecular Medicine; 3; 8-2021; 1-102689-1077CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.scivisionpub.com/pdfs/challenges-in-clinicogenetic-correlations-in-parkinsons-disease-pd-the-role-of-copy-number-variants-cnv-1817.pdfinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:21:09Zoai:ri.conicet.gov.ar:11336/149510instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:21:09.371CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Challenges in Clinico-Genetic Correlations in Parkinson’s disease (PD): The Role of Copy Number Variants (CNV)
title Challenges in Clinico-Genetic Correlations in Parkinson’s disease (PD): The Role of Copy Number Variants (CNV)
spellingShingle Challenges in Clinico-Genetic Correlations in Parkinson’s disease (PD): The Role of Copy Number Variants (CNV)
Gatto, Emilia Mabel
Parkinson Disease
Genetic Mosaicism.
Fluorescense-In-Situ-Hibridization
Copy Number Variant
title_short Challenges in Clinico-Genetic Correlations in Parkinson’s disease (PD): The Role of Copy Number Variants (CNV)
title_full Challenges in Clinico-Genetic Correlations in Parkinson’s disease (PD): The Role of Copy Number Variants (CNV)
title_fullStr Challenges in Clinico-Genetic Correlations in Parkinson’s disease (PD): The Role of Copy Number Variants (CNV)
title_full_unstemmed Challenges in Clinico-Genetic Correlations in Parkinson’s disease (PD): The Role of Copy Number Variants (CNV)
title_sort Challenges in Clinico-Genetic Correlations in Parkinson’s disease (PD): The Role of Copy Number Variants (CNV)
dc.creator.none.fl_str_mv Gatto, Emilia Mabel
Radrizzani Helguera, Martin
González Rojas, Natalia
Cesarini, Martin Emiliano
Etcheverry, José Luis
Perandones, Claudia
author Gatto, Emilia Mabel
author_facet Gatto, Emilia Mabel
Radrizzani Helguera, Martin
González Rojas, Natalia
Cesarini, Martin Emiliano
Etcheverry, José Luis
Perandones, Claudia
author_role author
author2 Radrizzani Helguera, Martin
González Rojas, Natalia
Cesarini, Martin Emiliano
Etcheverry, José Luis
Perandones, Claudia
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Parkinson Disease
Genetic Mosaicism.
Fluorescense-In-Situ-Hibridization
Copy Number Variant
topic Parkinson Disease
Genetic Mosaicism.
Fluorescense-In-Situ-Hibridization
Copy Number Variant
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Parkinson’s disease (PD) represents the second most common neurodegenerative disease and remains incurable. Mutations in multiple genes have been linked to monogenic PD (gPD); these monogenic forms, however, represent a small number of cases while in most instances PD appears as idiopathic (iPD). These findings raise the question of whether genetic and idiopathic parkinsonisms constitute the same disease. Nevertheless, monogenic-PD phenotypes and iPD both fulfill MDS criteria for PD, and show evidence of alpha-synuclein aggregates in both conditions. Distinct genetic loci in rare Mendelian forms have been identified as causal mutations, others as possible disease-causing genes, and genome-wide association studies have reported several risk loci, many of them located in the genes associated with the dominant mutations. Not only single-nucleotide polymorphisms (SNPs), but other kinds of DNA molecular defects as well have been spotted as significant disease-causing mutations, including large chromosomal structural rearrangements and copy number variations (CNVs). As their size varies, and detection methodologies have different sensitivity and resolution, CNVs pose a special challenge in genetic studies, and there currently is a debate on the pathogenetic or susceptibility impact of specific CNVs on PD. In this review, through multiple instances of experimental evidence, we analyze the impact on histopathology of the different mutational mechanisms involved in the genesis and etiology of PD. We believe that increasing our knowledge about the changes and implications at tissue level produced by each of those mechanisms will allow to develop much more suitable and personalized potential therapeutic strategies, biomarker identification, as well as disease modeling, agreeing with the precision medicine concept.
Fil: Gatto, Emilia Mabel. Instituto de Neurociencias Buenos Aires S. A.; Argentina
Fil: Radrizzani Helguera, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín; Argentina
Fil: González Rojas, Natalia. Instituto de Neurociencias Buenos Aires S. A.; Argentina
Fil: Cesarini, Martin Emiliano. Instituto de Neurociencias Buenos Aires S. A.; Argentina
Fil: Etcheverry, José Luis. Instituto de Neurociencias Buenos Aires S. A.; Argentina
Fil: Perandones, Claudia. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina
description Parkinson’s disease (PD) represents the second most common neurodegenerative disease and remains incurable. Mutations in multiple genes have been linked to monogenic PD (gPD); these monogenic forms, however, represent a small number of cases while in most instances PD appears as idiopathic (iPD). These findings raise the question of whether genetic and idiopathic parkinsonisms constitute the same disease. Nevertheless, monogenic-PD phenotypes and iPD both fulfill MDS criteria for PD, and show evidence of alpha-synuclein aggregates in both conditions. Distinct genetic loci in rare Mendelian forms have been identified as causal mutations, others as possible disease-causing genes, and genome-wide association studies have reported several risk loci, many of them located in the genes associated with the dominant mutations. Not only single-nucleotide polymorphisms (SNPs), but other kinds of DNA molecular defects as well have been spotted as significant disease-causing mutations, including large chromosomal structural rearrangements and copy number variations (CNVs). As their size varies, and detection methodologies have different sensitivity and resolution, CNVs pose a special challenge in genetic studies, and there currently is a debate on the pathogenetic or susceptibility impact of specific CNVs on PD. In this review, through multiple instances of experimental evidence, we analyze the impact on histopathology of the different mutational mechanisms involved in the genesis and etiology of PD. We believe that increasing our knowledge about the changes and implications at tissue level produced by each of those mechanisms will allow to develop much more suitable and personalized potential therapeutic strategies, biomarker identification, as well as disease modeling, agreeing with the precision medicine concept.
publishDate 2021
dc.date.none.fl_str_mv 2021-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/149510
Gatto, Emilia Mabel; Radrizzani Helguera, Martin; González Rojas, Natalia; Cesarini, Martin Emiliano; Etcheverry, José Luis; et al.; Challenges in Clinico-Genetic Correlations in Parkinson’s disease (PD): The Role of Copy Number Variants (CNV); SciVision Publishers; Genetics & Molecular Medicine; 3; 8-2021; 1-10
2689-1077
CONICET Digital
CONICET
url http://hdl.handle.net/11336/149510
identifier_str_mv Gatto, Emilia Mabel; Radrizzani Helguera, Martin; González Rojas, Natalia; Cesarini, Martin Emiliano; Etcheverry, José Luis; et al.; Challenges in Clinico-Genetic Correlations in Parkinson’s disease (PD): The Role of Copy Number Variants (CNV); SciVision Publishers; Genetics & Molecular Medicine; 3; 8-2021; 1-10
2689-1077
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.scivisionpub.com/pdfs/challenges-in-clinicogenetic-correlations-in-parkinsons-disease-pd-the-role-of-copy-number-variants-cnv-1817.pdf
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv SciVision Publishers
publisher.none.fl_str_mv SciVision Publishers
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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