dc.contributor.author | Benito Vicente, Asier | |
dc.contributor.author | Alves, Ana Catarina | |
dc.contributor.author | Etxebarria Gallego, Aitor | |
dc.contributor.author | Medeiros, Ana | |
dc.contributor.author | Martín Plágaro, César Augusto | |
dc.contributor.author | Bourbon, Mafalda | |
dc.date.accessioned | 2024-02-08T11:16:34Z | |
dc.date.available | 2024-02-08T11:16:34Z | |
dc.date.issued | 2015-12 | |
dc.identifier.citation | Genetics in Medicine 17 : 980-988 (2015) | |
dc.identifier.issn | 1098-3600 | |
dc.identifier.uri | http://hdl.handle.net/10810/65509 | |
dc.description.abstract | 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. | es_ES |
dc.description.sponsorship | Funding was obtained from the Portuguese Science and Technology Foundation (PTDC/SAU-GMG/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. | |
dc.language.iso | eng | es_ES |
dc.publisher | Nature | |
dc.relation | info:eu-repo/grantAgreement/MINECO/BFU 2012–36241 | |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.subject | functional studies | es_ES |
dc.subject | genetic diagnosis | |
dc.subject | integrated analysis | |
dc.subject | neutral alteration | |
dc.subject | pathogenic mutation | |
dc.title | The importance of an integrated analysis of clinical, molecular, and functional data for the genetic diagnosis of familial hypercholesterolemia | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © 2015. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.relation.publisherversion | https://www.nature.com/articles/gim201514 | |
dc.identifier.doi | 10.1038/gim.2015.14 | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
dc.identifier.eissn | 1530-0366 | |