Repository logo
 
Publication

Mutational analysis of a cohort with clinical diagnosis of familial hypercholesterolemia: considerations for genetic diagnosis improvement

2015-05-28Journal article Restricted access
Simple item page
dc.contributor.authorMedeiros, Ana Margarida
dc.contributor.authorAlves, Ana Catarina
dc.contributor.authorBourbon, Mafalda
dc.date.accessioned2015-08-07T11:58:00Z
dc.date.available2015-08-07T11:58:00Z
dc.date.issued2015-05-28
dc.description.abstractPURPOSE: Familial hypercholesterolemia (FH) is a common autosomal dominant disorder of lipid metabolism caused by mutations in LDLR, APOB, and PCSK9. To fulfill the World Health Organization recommendation, the Portuguese FH Study was established. Here, we report the results of the past 15 years and present practical considerations concerning the genetic diagnosis of FH based on our experience. METHODS: Our approach comprises a biochemical and molecular study and is divided into five phases, including the study of whole APOB and functional assays. RESULTS: A total of 2,122 individuals were enrolled. A putative pathogenic variant was identified in 660 heterozygous patients: LDLR (623), APOB (33), and PCSK9 (4); 8 patients presented with homozygous FH. A detection rate of 41.5% was observed. A stricter biochemical criteria was shown to improve patient identification. Overall, we have identified 3.4% and 80% of all heterozygous and homozygous patients, respectively, estimated to exist in our country. CONCLUSION: The Portuguese FH Study has established the genetic diagnosis of FH in Portugal and is committed to continue the investigation of the genetic complexity of FH. Genetic diagnosis of FH should be expanded to include the study of all coding/flanking regions of APOB and functional in vitro studies, to improve the correct patient identification, and to avoid misdiagnosis.por
dc.description.sponsorshipFunding was obtained from the Portuguese Cardiology Society (project grant D13123) and Science and Technology Foundation (project grant PIC/IC/83333/2007). A.C.A. was supported by a PhD student grant (SFRH/BD/27990/2006). A.M.M. was supported by a research grant from the National Institute of Health Doutor Ricardo Jorge (BRJ-DPS/2012).por
dc.identifier.citationGenet Med. 2016 Apr;18(4):316-24. doi: 10.1038/gim.2015.71. Epub 2015 May 28por
dc.identifier.doi10.1038/gim.2015.71
dc.identifier.issn0047-2506
dc.identifier.otherESSN: 1478-6990
dc.identifier.urihttp://hdl.handle.net/10400.18/3107
dc.language.isoengpor
dc.publisherNature Publishing Group / American College of Medical Genetics and Genomicspor
dc.relationproject grant PIC/IC/83333/2007-FCTpor
dc.relationproject grant D13123-SPCpor
dc.relation.publisherversionhttp://www.nature.com/gim/journal/vaop/ncurrent/full/gim201571a.htmlpor
dc.subjectAPOBpor
dc.subjectFamilial Hypercholesterolemiapor
dc.subjectFunctional Assayspor
dc.subjectLDLRpor
dc.subjectPCSK9por
dc.subjectDoenças Cardio e Cérebro-vascularespor
dc.subjectHipercolesterolemia Familiarpor
dc.subjectSaúde Pública
dc.subjectPortugal
dc.titleMutational analysis of a cohort with clinical diagnosis of familial hypercholesterolemia: considerations for genetic diagnosis improvementpor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.titleGenetics in Medicinepor
rcaap.rightsembargoedAccesspor
rcaap.typearticlepor

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
Mutational analysis of a cohort with clinical diagnosis of familial hypercholesterolemia.pdf
Size:
345.33 KB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
1.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

DPSPDNT - Artigos em revistas internacionais