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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/149510
Ver los metadatos del registro completo
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CONICET Digital (CONICET) |
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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 |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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13.070432 |