Validation of LDLr Activity as a Tool to Improve Genetic Diagnosis of Familial Hypercholesterolemia: A Retrospective on Functional Characterization of LDLr Variants

Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by high blood-cholesterol levels mostly caused by mutations in the low-density lipoprotein receptor (LDLr). With a prevalence as high as 1/200 in some populations, genetic screening for pathogenic LDLr mutations is a...

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Detalhes bibliográficos
Autores: Benito-Vicente, Asier, Uribe, Kepa B., Jebari-Benslaiman, Shifa, Galicia-García, Unai, Ostolaza, Helena, Martín, César
Tipo de documento: artigo
Data de publicação:2018
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/397587
Acesso em linha:http://hdl.handle.net/10261/397587
https://api.elsevier.com/content/abstract/scopus_id/85048291407
Access Level:Acceso aberto
Palavra-chave:Low Density Lipoprotein receptor (LDLr)
Familial hypercholesterolemia
Functional validation
In vitro
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spelling Validation of LDLr Activity as a Tool to Improve Genetic Diagnosis of Familial Hypercholesterolemia: A Retrospective on Functional Characterization of LDLr VariantsBenito-Vicente, AsierUribe, Kepa B.Jebari-Benslaiman, ShifaGalicia-García, UnaiOstolaza, HelenaMartín, CésarLow Density Lipoprotein receptor (LDLr)Familial hypercholesterolemiaFunctional validationIn vitroFamilial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by high blood-cholesterol levels mostly caused by mutations in the low-density lipoprotein receptor (LDLr). With a prevalence as high as 1/200 in some populations, genetic screening for pathogenic LDLr mutations is a cost-effective approach in families classified as 'definite' or 'probable' FH and can help to early diagnosis. However, with over 2000 LDLr variants identified, distinguishing pathogenic mutations from benign mutations is a long-standing challenge in the field. In 1998, the World Health Organization (WHO) highlighted the importance of improving the diagnosis and prognosis of FH patients thus, identifying LDLr pathogenic variants is a longstanding challenge to provide an accurate genetic diagnosis and personalized treatments. In recent years, accessible methodologies have been developed to assess LDLr activity in vitro, providing experimental reproducibility between laboratories all over the world that ensures rigorous analysis of all functional studies. In this review we present a broad spectrum of functionally characterized missense LDLr variants identified in patients with FH, which is mandatory for a definite diagnosis of FH.Peer reviewedMultidisciplinary Digital Publishing InstituteConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252018info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_dcae04bcapplication/pdfhttp://hdl.handle.net/10261/397587https://api.elsevier.com/content/abstract/scopus_id/85048291407reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.3390/ijms19061676Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3975872026-05-22T06:33:51Z
dc.title.none.fl_str_mv Validation of LDLr Activity as a Tool to Improve Genetic Diagnosis of Familial Hypercholesterolemia: A Retrospective on Functional Characterization of LDLr Variants
title Validation of LDLr Activity as a Tool to Improve Genetic Diagnosis of Familial Hypercholesterolemia: A Retrospective on Functional Characterization of LDLr Variants
spellingShingle Validation of LDLr Activity as a Tool to Improve Genetic Diagnosis of Familial Hypercholesterolemia: A Retrospective on Functional Characterization of LDLr Variants
Benito-Vicente, Asier
Low Density Lipoprotein receptor (LDLr)
Familial hypercholesterolemia
Functional validation
In vitro
title_short Validation of LDLr Activity as a Tool to Improve Genetic Diagnosis of Familial Hypercholesterolemia: A Retrospective on Functional Characterization of LDLr Variants
title_full Validation of LDLr Activity as a Tool to Improve Genetic Diagnosis of Familial Hypercholesterolemia: A Retrospective on Functional Characterization of LDLr Variants
title_fullStr Validation of LDLr Activity as a Tool to Improve Genetic Diagnosis of Familial Hypercholesterolemia: A Retrospective on Functional Characterization of LDLr Variants
title_full_unstemmed Validation of LDLr Activity as a Tool to Improve Genetic Diagnosis of Familial Hypercholesterolemia: A Retrospective on Functional Characterization of LDLr Variants
title_sort Validation of LDLr Activity as a Tool to Improve Genetic Diagnosis of Familial Hypercholesterolemia: A Retrospective on Functional Characterization of LDLr Variants
dc.creator.none.fl_str_mv Benito-Vicente, Asier
Uribe, Kepa B.
Jebari-Benslaiman, Shifa
Galicia-García, Unai
Ostolaza, Helena
Martín, César
author Benito-Vicente, Asier
author_facet Benito-Vicente, Asier
Uribe, Kepa B.
Jebari-Benslaiman, Shifa
Galicia-García, Unai
Ostolaza, Helena
Martín, César
author_role author
author2 Uribe, Kepa B.
Jebari-Benslaiman, Shifa
Galicia-García, Unai
Ostolaza, Helena
Martín, César
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Low Density Lipoprotein receptor (LDLr)
Familial hypercholesterolemia
Functional validation
In vitro
topic Low Density Lipoprotein receptor (LDLr)
Familial hypercholesterolemia
Functional validation
In vitro
description Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by high blood-cholesterol levels mostly caused by mutations in the low-density lipoprotein receptor (LDLr). With a prevalence as high as 1/200 in some populations, genetic screening for pathogenic LDLr mutations is a cost-effective approach in families classified as 'definite' or 'probable' FH and can help to early diagnosis. However, with over 2000 LDLr variants identified, distinguishing pathogenic mutations from benign mutations is a long-standing challenge in the field. In 1998, the World Health Organization (WHO) highlighted the importance of improving the diagnosis and prognosis of FH patients thus, identifying LDLr pathogenic variants is a longstanding challenge to provide an accurate genetic diagnosis and personalized treatments. In recent years, accessible methodologies have been developed to assess LDLr activity in vitro, providing experimental reproducibility between laboratories all over the world that ensures rigorous analysis of all functional studies. In this review we present a broad spectrum of functionally characterized missense LDLr variants identified in patients with FH, which is mandatory for a definite diagnosis of FH.
publishDate 2018
dc.date.none.fl_str_mv 2018
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_dcae04bc
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/397587
https://api.elsevier.com/content/abstract/scopus_id/85048291407
url http://hdl.handle.net/10261/397587
https://api.elsevier.com/content/abstract/scopus_id/85048291407
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://doi.org/10.3390/ijms19061676
Sí
dc.rights.none.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 Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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