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The familial hypercholesterolaemia phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causes

2019-12-19Journal article Restricted access
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dc.contributor.authorMariano, C.
dc.contributor.authorAlves, A.C.
dc.contributor.authorMedeiros, A.
dc.contributor.authorChora, J.R.
dc.contributor.authorAntunes, M.
dc.contributor.authorFutema, M.
dc.contributor.authorHumphries, S.E.
dc.contributor.authorBourbon, M.
dc.date.accessioned2020-04-30T20:55:10Z
dc.date.available2020-04-30T20:55:10Z
dc.date.issued2019-12-19
dc.description.abstractFamilial Hypercholesterolaemia (FH) is a monogenic disorder characterised by high LDL-C concentrations and increased cardiovascular risk. However, in clinically defined FH cohorts worldwide, an FH-causing variant is only found in 40-50% of the cases. The aim of this work was to characterise the genetic cause of the FH phenotype in Portuguese clinical FH patients. Methods and Results Between 1999 and 2017, 731 index patients (311 children and 420 adults) who met the Simon Broome diagnostic criteria had been referred to our laboratory. LDLR, APOB, PCSK9, APOE, LIPA, LDLRAP1, ABCG5/8 genes were analysed by PCR amplification and Sanger sequencing. The 6-SNP LDL-C genetic risk score (GRS) for polygenic hypercholesterolaemia was validated in the Portuguese population and cases with a GRS over the 25th percentile were considered to have a high likelihood of polygenic hypercholesterolaemia. An FH-causing mutation was found in 39% of patients (94% in LDLR, 5% APOB and 1% PCSK9), while at least 29% have polygenic hypercholesterolaemia and 1% have other lipid disorders. A genetic cause for the FH phenotype was found in 503 patients (69%). All known causes of the FH phenotype should be investigated in FH cohorts to ensure accurate diagnosis and appropriate management.pt_PT
dc.description.sponsorshipCibelle Mariano was supported by a PhD student grant [SFRH/BD/52494/2014]. Marta Futema is supported by the Fondation Leducq Transatlantic Networks of Excellence Program grant (no 14 CVD03). The work of Marilia Antunes is partially funded by UID/MAT/000016/2019. SEH acknowledges funding from the British Heart Foundation grant (BHF PG08/008) and from the NIHR UCLH BRC. MB acknowledges funding from Science and Technology Foundation (PIC/IC/83020/2007) (PIC/IC/83333/2007) for the e_COR and Portuguese FH Study and from Portuguese Cardiology Society for the Portuguese FH Study.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationClin Genet. 2020 Mar;97(3):457-466. doi: 10.1111/cge.13697. Epub 2019 Dec 31pt_PT
dc.identifier.doi10.1111/cge.13697pt_PT
dc.identifier.issn0009-9163
dc.identifier.urihttp://hdl.handle.net/10400.18/6563
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherJohn Wiley and Sonspt_PT
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/doi/abs/10.1111/cge.13697pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/pt_PT
dc.subjectFamilial Hypercholesterolaemiapt_PT
dc.subjectGenetic Risk Scorept_PT
dc.subjectMonogenic Dyslipidaemiapt_PT
dc.subjectPhenocopiespt_PT
dc.subjectPolygenic Hypercholesterolaemiapt_PT
dc.subjectHipercolesterolemia Familiarpt_PT
dc.subjectDoenças Cardio e Cérebro-vascularespt_PT
dc.titleThe familial hypercholesterolaemia phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causespt_PT
dc.title.alternativeThe FH phenotype: monogenic familial hypercholesterolaemia, polygenic hypercholesterolaemia and other causespt_PT
dc.title.alternativeFH phenotype: monogenic, polygenic and other causespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5646-ICCMS/PIC%2FIC%2F83020%2F2007/PT
oaire.citation.endPage466pt_PT
oaire.citation.issue3pt_PT
oaire.citation.startPage457pt_PT
oaire.citation.titleClinical Geneticspt_PT
oaire.citation.volume97pt_PT
oaire.fundingStream5646-ICCMS
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctDe acordo com política editorial da revista.pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublication6db57903-0519-4d9e-81fd-974dd1940566
relation.isProjectOfPublication.latestForDiscovery6db57903-0519-4d9e-81fd-974dd1940566

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