Low-density lipoprotein receptor mutational analysis in diagnosis of familial hypercholesterolemia
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.18/4820 |
Resumo: | PURPOSE OF REVIEW: To present up to date evidence on the pathogenicity of low-density lipoprotein receptor (LDLR) variants and to propose a strategy that is suitable for implementation in the clinical work-up of familial hypercholesterolaemia. RECENT FINDINGS: More than 1800 variants have been described in the LDLR gene of patients with a clinical diagnosis of familial hypercholesterolaemia; however, less than 15% have functional evidence of pathogenicity. SUMMARY: The spectrum of variants in the LDLR identified in patients with clinical familial hypercholesterolaemia is increasing as novel variants are still being reported. However, over 50% of all LDLR variants need further evidence before they can be confirmed as mutations causing disease. Even with applying the recent American College of Medical Genetics variant classification, a large number of variants are still considered variants of unknown significance. Before obtaining an undisputable confirmation of the effect on the expression and activity of the LDLR, reporting these variants as part of a clinical diagnosis to the patient holds the risk that it might need to be withdrawn in a later stage. An investment should be made to develop functional assays to characterize LDLR variants of unknown significance for a better patient diagnosis and to prevent confusion in the physician's office. |
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Low-density lipoprotein receptor mutational analysis in diagnosis of familial hypercholesterolemiaFunctional StudiesLDL Receptor ActivityLDLR genePatient DiagnosisDoenças Cardio e Cérebro-vascularesPURPOSE OF REVIEW: To present up to date evidence on the pathogenicity of low-density lipoprotein receptor (LDLR) variants and to propose a strategy that is suitable for implementation in the clinical work-up of familial hypercholesterolaemia. RECENT FINDINGS: More than 1800 variants have been described in the LDLR gene of patients with a clinical diagnosis of familial hypercholesterolaemia; however, less than 15% have functional evidence of pathogenicity. SUMMARY: The spectrum of variants in the LDLR identified in patients with clinical familial hypercholesterolaemia is increasing as novel variants are still being reported. However, over 50% of all LDLR variants need further evidence before they can be confirmed as mutations causing disease. Even with applying the recent American College of Medical Genetics variant classification, a large number of variants are still considered variants of unknown significance. Before obtaining an undisputable confirmation of the effect on the expression and activity of the LDLR, reporting these variants as part of a clinical diagnosis to the patient holds the risk that it might need to be withdrawn in a later stage. An investment should be made to develop functional assays to characterize LDLR variants of unknown significance for a better patient diagnosis and to prevent confusion in the physician's office.The MB research has been supported by grants from the Portuguese Cardiology Society, Science and Technology Foundation and BioISI, centre grant UID/MULTI/ 04046/2013, from FCT/MCTES/PIDDAC, Portugal.Wolters Kluwer Health, IncRepositório Científico do Instituto Nacional de SaúdeBourbon, M.Alves, A.C.Sijbrands, E.J.2017-11-03T16:49:21Z2017-042017-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/4820engCurr Opin Lipidol. 2017 Apr;28(2):120-129. doi: 10.1097/MOL.0000000000000404.0957-967210.1097/MOL.0000000000000404info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:40:28Zoai:repositorio.insa.pt:10400.18/4820Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:39:28.176147Repositório 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 |
Low-density lipoprotein receptor mutational analysis in diagnosis of familial hypercholesterolemia |
title |
Low-density lipoprotein receptor mutational analysis in diagnosis of familial hypercholesterolemia |
spellingShingle |
Low-density lipoprotein receptor mutational analysis in diagnosis of familial hypercholesterolemia Bourbon, M. Functional Studies LDL Receptor Activity LDLR gene Patient Diagnosis Doenças Cardio e Cérebro-vasculares |
title_short |
Low-density lipoprotein receptor mutational analysis in diagnosis of familial hypercholesterolemia |
title_full |
Low-density lipoprotein receptor mutational analysis in diagnosis of familial hypercholesterolemia |
title_fullStr |
Low-density lipoprotein receptor mutational analysis in diagnosis of familial hypercholesterolemia |
title_full_unstemmed |
Low-density lipoprotein receptor mutational analysis in diagnosis of familial hypercholesterolemia |
title_sort |
Low-density lipoprotein receptor mutational analysis in diagnosis of familial hypercholesterolemia |
author |
Bourbon, M. |
author_facet |
Bourbon, M. Alves, A.C. Sijbrands, E.J. |
author_role |
author |
author2 |
Alves, A.C. Sijbrands, E.J. |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
dc.contributor.author.fl_str_mv |
Bourbon, M. Alves, A.C. Sijbrands, E.J. |
dc.subject.por.fl_str_mv |
Functional Studies LDL Receptor Activity LDLR gene Patient Diagnosis Doenças Cardio e Cérebro-vasculares |
topic |
Functional Studies LDL Receptor Activity LDLR gene Patient Diagnosis Doenças Cardio e Cérebro-vasculares |
description |
PURPOSE OF REVIEW: To present up to date evidence on the pathogenicity of low-density lipoprotein receptor (LDLR) variants and to propose a strategy that is suitable for implementation in the clinical work-up of familial hypercholesterolaemia. RECENT FINDINGS: More than 1800 variants have been described in the LDLR gene of patients with a clinical diagnosis of familial hypercholesterolaemia; however, less than 15% have functional evidence of pathogenicity. SUMMARY: The spectrum of variants in the LDLR identified in patients with clinical familial hypercholesterolaemia is increasing as novel variants are still being reported. However, over 50% of all LDLR variants need further evidence before they can be confirmed as mutations causing disease. Even with applying the recent American College of Medical Genetics variant classification, a large number of variants are still considered variants of unknown significance. Before obtaining an undisputable confirmation of the effect on the expression and activity of the LDLR, reporting these variants as part of a clinical diagnosis to the patient holds the risk that it might need to be withdrawn in a later stage. An investment should be made to develop functional assays to characterize LDLR variants of unknown significance for a better patient diagnosis and to prevent confusion in the physician's office. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-11-03T16:49:21Z 2017-04 2017-04-01T00:00:00Z |
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/10400.18/4820 |
url |
http://hdl.handle.net/10400.18/4820 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Curr Opin Lipidol. 2017 Apr;28(2):120-129. doi: 10.1097/MOL.0000000000000404. 0957-9672 10.1097/MOL.0000000000000404 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Wolters Kluwer Health, Inc |
publisher.none.fl_str_mv |
Wolters Kluwer Health, Inc |
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 |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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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1799132134383812608 |