Repository logo
 
Publication

Characterization of Two Variants at Met 1 of the Human LDLR Gene Encoding the Same Amino Acid but Causing Different Functional Phenotypes

2021-09-14Journal article Open access
Simple item page
dc.contributor.authorGraça, Rafael
dc.contributor.authorFernandes, Rafael
dc.contributor.authorAlves, Ana catarina
dc.contributor.authorMenezes, Juliane
dc.contributor.authorRomão, Luísa
dc.contributor.authorBourbon, Mafalda
dc.date.accessioned2022-02-07T16:15:39Z
dc.date.available2022-02-07T16:15:39Z
dc.date.issued2021-09-14
dc.descriptionThis article belongs to the Special Issue mRNA Metabolism in Health and Disease.pt_PT
dc.description.abstractFamilial hypercholesterolemia (FH) is the most common genetic disorder of lipid metabolism, characterized by increased levels of total and LDL plasma cholesterol, which leads to premature atherosclerosis and coronary heart disease. FH phenotype has considerable genetic heterogeneity and phenotypic variability, depending on LDL receptor activity and lifestyle. To improve diagnosis and patient management, here, we characterized two single nucleotide missense substitutions at Methionine 1 of the human LDLR gene (c.1A>T/p.(Met1Leu) and c.1A>C/p.(Met1Leu)). We used a combination of Western blot, flow cytometry, and luciferase assays to determine the effects of both variants on the expression, activity, and synthesis of LDLR. Our data show that both variants can mediate translation initiation, although the expression of variant c.1A>T is very low. Both variants are in the translation initiation codon and codify for the same amino acid p.(Met1Leu), yet they lead to different levels of impairment on LDLR expression and activity, corroborating different efficiencies of the translation initiation at these non-canonical initiation codons. The functional data of these variants allowed for an improved American College of Medical Genetics (ACMG) classification for both variants, which can allow a more personalized choice of the lipid-lowering treatment and dyslipidemia management, ultimately improving patients' prognosis.pt_PT
dc.description.sponsorshipThe authors acknowledge Fundação para a Ciência e a Tecnologia (Ph.D. scholarship no. SFRH/PD/BD/131427/2017 and SFRH/PD/BD/114392/2016).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationBiomedicines. 2021 Sep 14;9(9):1219. doi: 10.3390/biomedicines9091219pt_PT
dc.identifier.doi10.3390/biomedicines9091219pt_PT
dc.identifier.issn2227-9059
dc.identifier.urihttp://hdl.handle.net/10400.18/7939
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationFCT/SFRH/PD/BD/131427/2017pt_PT
dc.relationFCT/SFRH/PD/BD/114392/2016pt_PT
dc.relation.publisherversionhttps://www.mdpi.com/2227-9059/9/9/1219pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectACMG Classificationpt_PT
dc.subjectLDLRpt_PT
dc.subjectFamilial Hypercholesterolemiapt_PT
dc.subjectFunctional Characterizationpt_PT
dc.subjectInitiation Codonpt_PT
dc.subjectGenómica Funcionalpt_PT
dc.subjectGenómica Funcional e Estruturalpt_PT
dc.subjectDoenças Genéticaspt_PT
dc.subjectDoenças Cardio e Cérebro-vasculares
dc.titleCharacterization of Two Variants at Met 1 of the Human LDLR Gene Encoding the Same Amino Acid but Causing Different Functional Phenotypespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue9pt_PT
oaire.citation.startPage1219pt_PT
oaire.citation.titleBiomedicinespt_PT
oaire.citation.volume9pt_PT
person.familyNameRomão
person.givenNameLuísa
person.identifierhttps://scholar.google.pt/citations?hl=pt-PT&user=CAHjIsoAAAAJ&cstart=60&pagesize=20
person.identifier.ciencia-idEB19-DF07-EB37
person.identifier.orcid0000-0002-5061-5287
person.identifier.scopus-author-idhttp://www.scopus.com/authid/detail.url?authorId=6602834878
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicatione2eb8254-24ed-4bfc-b478-3e9022f729e2
relation.isAuthorOfPublication.latestForDiscoverye2eb8254-24ed-4bfc-b478-3e9022f729e2

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Graça et al. 2021.pdf
Size:
855.59 KB
Format:
Adobe Portable Document Format
Download

Collections

DGH - Artigos em revistas internacionais
DPSPDNT - Artigos em revistas internacionais