The importance of an integrated analysis of clinical, molecular, and functional data for the genetic diagnosis of familial hypercholesterolemia

Detalhes bibliográficos
Autor(a) principal: Benito-Vicente, A.
Data de Publicação: 2015
Outros Autores: Alves, A.C, Etxebarria, A., Medeiros, A.M., Martin, C., Bourbon, M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.18/3092
Resumo: The authors thank Rocío Alonso for excellent technical assistance. They are also grateful to A. Gómez-Muñoz for making flow cytometry facilities available and SGIker (Analytical and High-Resolution Microscopy in Biomedicine Service of the UPV/ EHU) and Monty Krieger for kindly providing CHO-ldlA7 cells. Capillary sequencing was performed at Unidade de Tecnologia e Inovação (Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge).
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spelling The importance of an integrated analysis of clinical, molecular, and functional data for the genetic diagnosis of familial hypercholesterolemiaFunctional StudiesGenetic DiagnosisIntegrated AnalysisNeutral AlterationPathogenic MutationDoenças Cardio e Cérebro-vascularesThe authors thank Rocío Alonso for excellent technical assistance. They are also grateful to A. Gómez-Muñoz for making flow cytometry facilities available and SGIker (Analytical and High-Resolution Microscopy in Biomedicine Service of the UPV/ EHU) and Monty Krieger for kindly providing CHO-ldlA7 cells. Capillary sequencing was performed at Unidade de Tecnologia e Inovação (Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge).Purpose: Familial hypercholesterolemia (FH) is one of the most common monogenic disorders, and the high concentrations of low-density lipoprotein (LDL) cholesterol presented since birth confers on these patients an increased cardiovascular risk. More than 1,600 alterations have been described in the LDL receptor gene (LDLR), but a large number need to be validated as mutations causing disease to establish a diagnosis of FH. This study aims to characterize, both at the phenotypic and genotypic levels, families with a clinical diagnosis of FH and present evidence for the importance of the integration of clinical, molecular, and functional data for the correct diagnosis of patients with FH.Methods:A detailed analysis of the phenotype and genotype presented by 55 families with 13 different alterations in the LDLR was conducted. For eight of these, an extensive functional characterization was performed by flow cytometry, confocal microscopy, and reverse transcriptase polymerase chain reaction.Results:Carriers of neutral alterations presented a significantly lower incidence of premature cardiovascular disease, lower levels of atherogenic lipoproteins and a large number of these individuals had LDL-cholesterol values below the 75th percentile. presented a significantly lower incidence of premature cardiovascular disease, lower levels of atherogenic lipoproteins and a large number of these individuals had LDL-cholesterol values below the 75th percentile However, the functional study was essential to determine the pathogenicity of variants.Conclusion:The data collected illustrate the importance of this integrated analysis for the correct assessment of patients with FH who can otherwise be misdiagnosed.Funding was obtained from the Portuguese Science and Technology Foundation (PTDC/SAUGMG/101874/2008), the Spanish Ministry of Economy and Competitiveness (grant BFU 2012–36241), and Programa INNPACTO (grant IPT-2011-0817-010000). A.C.A. was supported by a PhD student grant (SFRH/BD/27990/2006) and a research grant from PTDC/SAU-GMG/101874/2008.Nature Publishing Group/American College of Medical Genetics and GenomicsRepositório Científico do Instituto Nacional de SaúdeBenito-Vicente, A.Alves, A.CEtxebarria, A.Medeiros, A.M.Martin, C.Bourbon, M.2015-06-26T13:50:07Z2015-03-052015-03-05T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/3092engGenet Med. 2015 Dec;17(12):980-8. doi: 10.1038/gim.2015.14. Epub 2015 Mar 51098-3600gim.2015.14info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:39:33Zoai:repositorio.insa.pt:10400.18/3092Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:37:56.848597Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv The importance of an integrated analysis of clinical, molecular, and functional data for the genetic diagnosis of familial hypercholesterolemia
title The importance of an integrated analysis of clinical, molecular, and functional data for the genetic diagnosis of familial hypercholesterolemia
spellingShingle The importance of an integrated analysis of clinical, molecular, and functional data for the genetic diagnosis of familial hypercholesterolemia
Benito-Vicente, A.
Functional Studies
Genetic Diagnosis
Integrated Analysis
Neutral Alteration
Pathogenic Mutation
Doenças Cardio e Cérebro-vasculares
title_short The importance of an integrated analysis of clinical, molecular, and functional data for the genetic diagnosis of familial hypercholesterolemia
title_full The importance of an integrated analysis of clinical, molecular, and functional data for the genetic diagnosis of familial hypercholesterolemia
title_fullStr The importance of an integrated analysis of clinical, molecular, and functional data for the genetic diagnosis of familial hypercholesterolemia
title_full_unstemmed The importance of an integrated analysis of clinical, molecular, and functional data for the genetic diagnosis of familial hypercholesterolemia
title_sort The importance of an integrated analysis of clinical, molecular, and functional data for the genetic diagnosis of familial hypercholesterolemia
author Benito-Vicente, A.
author_facet Benito-Vicente, A.
Alves, A.C
Etxebarria, A.
Medeiros, A.M.
Martin, C.
Bourbon, M.
author_role author
author2 Alves, A.C
Etxebarria, A.
Medeiros, A.M.
Martin, C.
Bourbon, M.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório Científico do Instituto Nacional de Saúde
dc.contributor.author.fl_str_mv Benito-Vicente, A.
Alves, A.C
Etxebarria, A.
Medeiros, A.M.
Martin, C.
Bourbon, M.
dc.subject.por.fl_str_mv Functional Studies
Genetic Diagnosis
Integrated Analysis
Neutral Alteration
Pathogenic Mutation
Doenças Cardio e Cérebro-vasculares
topic Functional Studies
Genetic Diagnosis
Integrated Analysis
Neutral Alteration
Pathogenic Mutation
Doenças Cardio e Cérebro-vasculares
description The authors thank Rocío Alonso for excellent technical assistance. They are also grateful to A. Gómez-Muñoz for making flow cytometry facilities available and SGIker (Analytical and High-Resolution Microscopy in Biomedicine Service of the UPV/ EHU) and Monty Krieger for kindly providing CHO-ldlA7 cells. Capillary sequencing was performed at Unidade de Tecnologia e Inovação (Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge).
publishDate 2015
dc.date.none.fl_str_mv 2015-06-26T13:50:07Z
2015-03-05
2015-03-05T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.18/3092
url http://hdl.handle.net/10400.18/3092
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Genet Med. 2015 Dec;17(12):980-8. doi: 10.1038/gim.2015.14. Epub 2015 Mar 5
1098-3600
gim.2015.14
dc.rights.driver.fl_str_mv info:eu-repo/semantics/embargoedAccess
eu_rights_str_mv embargoedAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group/American College of Medical Genetics and Genomics
publisher.none.fl_str_mv Nature Publishing Group/American College of Medical Genetics and Genomics
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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