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Characterization of the First PCSK9 Gain of Function Homozygote

2015-11-10Journal article Restricted access
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dc.contributor.authorAlves, Ana Catarina
dc.contributor.authorEtxebarria, Aitor
dc.contributor.authorMedeiros, Ana Margarida
dc.contributor.authorBenito-Vicente, Asier
dc.contributor.authorThedrez, Aurélie
dc.contributor.authorPassard, Maxime
dc.contributor.authorCroyal, Mikaël
dc.contributor.authorMartin, Cesar
dc.contributor.authorLambert, Gilles
dc.contributor.authorBourbon, Mafalda
dc.date.accessioned2016-02-02T16:41:13Z
dc.date.available2016-02-02T16:41:13Z
dc.date.issued2015-11-10
dc.descriptionLetterpt_PT
dc.description.abstractGain of function (GOF) mutations in proprotein convertase subtilisin kexin type 9 (PCSK9) are a rare cause of familial hypercholesterolemia (FH). We identified a child with a clinical diagnosis of FH with 2 novel putative PCSK9 GOF missense variants (p.[(Ala62Asp)]; [(Pro467Ala)]), and no mutation in the low-density lipoprotein (LDL) receptor (LDLR) or in apolipoprotein B100 (APOB) genes. The proband was referred to the Portuguese FH Study (1) at age 11 and presented a total cholesterol of 316 mg/dl and low-density lipoprotein cholesterol (LDL-C) of 234 mg/dl on a strict diet. The phenotype presented by all PCSK9 heterozygous carriers within this large pedigree is similar to APOB heterozygous carriers (LDL-C, 198.75 ± 14.98 mg/dl vs. LDL-C, 211.57 ± 42.02 mg/dl; p = 0.227) but significantly different than heterozygous LDLR carriers (LDL-C, 198.75 ± 14.98 mg/dl vs. LDL-C, 230.63 ± 76.50 mg/dl; p = 0.012) when comparing the relatives’ phenotype in our cohort.
dc.description.sponsorshipFunding was obtained from the Portuguese Science and Technology Foundation (FCT) (PTDC/SAU-GMG/101874/2008) (to Dr. Bourbon), from the Spanish Ministry of Economy and Competitiveness (grant N° BFU 2012-36241) and Programa INNPACTO (grant N° IPT-2011-0817-010000) (to Dr. Martin), and from the Agence Nationale de la Recherche (Programme Blanc BCNCT) (to Dr. Lambert). Dr. Alves was a recipient of a PhD grant SFRH/BD/27990/2006 and research grant PTDC/SAU-GMG/101874/2008 from FCT. Mrs. Medeiros was supported by a research grant from the National Institute of Health Doutor Ricardo Jorge (BRJ-DPS/2012). Mr. Benito-Vicente was supported by a grant PIF (2014/2015) Gobierno Vasco. Alirocumab was obtained from Sanofi-Regeneron. Dr. Lambert has received honoraria from Sanofi-Regeneron, Amgen, and Pfizer and research funding from Sanofi-Regeneron. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Alves and Etxebarria contributed equally to this work.
dc.identifier.citationJ Am Coll Cardiol. 2015 Nov 10;66(19):2152-4. doi: 10.1016/j.jacc.2015.08.871. Epub 2015 Nov 2.pt_PT
dc.identifier.doi10.1016/j.jacc.2015.08.871pt_PT
dc.identifier.issn2045-2322
dc.identifier.urihttp://hdl.handle.net/10400.18/3277
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevier/ American College of Cardiology Foundationpt_PT
dc.relationNovel genes causing Familial Hypercholesterolaemia
dc.relation.publisherversionhttp://content.onlinejacc.org/article.aspx?articleid=2468518pt_PT
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S073510971506057X
dc.subjectFamilial Hypercholesterolemiapt_PT
dc.subjectHomozygotept_PT
dc.subjectPCSK9
dc.subjectPCSK9 protein, human
dc.subjectDNA/genetics
dc.subjectDNA
dc.subjectPortugal
dc.subjectDoenças Cardio e Cérebro-vasculares
dc.subjectHipercolesterolemia Familiar
dc.titleCharacterization of the First PCSK9 Gain of Function Homozygotept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleNovel genes causing Familial Hypercholesterolaemia
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-GMG%2F101874%2F2008/PT
oaire.citation.endPage2154pt_PT
oaire.citation.startPage2152pt_PT
oaire.citation.volume66(19)pt_PT
oaire.fundingStream3599-PPCDT
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationf2cced4d-dbf7-43c7-98a7-a370b6dbb952
relation.isProjectOfPublication.latestForDiscoveryf2cced4d-dbf7-43c7-98a7-a370b6dbb952

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