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Familial thrombotic risk based on the genetic background of Protein C Deficiency in a Portuguese Study

2015-10Journal article Open access
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dc.contributor.authorFidalgo, T
dc.contributor.authorMartinho, P
dc.contributor.authorSalvado, R
dc.contributor.authorManco, L
dc.contributor.authorOliveira, AC
dc.contributor.authorPinto, CS
dc.contributor.authorGonçalves, E
dc.contributor.authorMarques, D
dc.contributor.authorSevivas, T
dc.contributor.authorMartins, N
dc.contributor.authorRibeiro, ML
dc.date.accessioned2018-11-28T13:01:42Z
dc.date.available2018-11-28T13:01:42Z
dc.date.issued2015-10
dc.description.abstractINTRODUCTION: Inherited protein C (PC) deficiency is a well-known risk factor for venous thrombosis (VT). Plasma PC levels are reliable in moderate to severe deficiencies; however, in mildly deficient individuals, the levels may overlap with those considered normal. Genetic studies of PROC, which encodes PC, could help identify carriers; genome-wide association studies (GWAS) have shown that approximately 50% of phenotypic variation in PC deficiency is caused by the cumulative effects of mutations in several other loci, namely in the PROCR. PATIENTS AND METHODS: With the main objective of determining the genotype/phenotype correlation in 59 Portuguese individuals from 26 unrelated families with history of thrombosis and repeatedly low/borderline PC plasma levels, we conducted a molecular study by direct sequencing of PROC; PROC promoter haplotypes and PROCR c.4600A>G polymorphism (rs867186), which are known to influence plasma PC concentrations, were also screened. RESULTS: Twelve different PROC mutations were identified, one of them not previously reported, p.Cys105Arg. The mutation types and locations as well as haplotype combinations correlated with the phenotypic severity. The most frequent mutation, p.Arg199X, correlated with the CGTC haplotype and was identified in nine families containing patients with higher numbers of VT episodes. This mutation in homozygous individuals for the CGTC haplotype is a significant risk factor for VT in Portuguese. CONCLUSION: These genetic family studies allowed the identification of the unknown carriers and individuals at a higher thrombotic risk within each family, thus permitting the evaluation of the need for prophylactic measures, particularly in at-risk situations.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationEur J Haematol. 2015 Oct;95(4):294-307.pt_PT
dc.identifier.doi10.1111/ejh.12488pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.4/2184
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectPredisposição Genética para Doençapt_PT
dc.subjectProteína Cpt_PT
dc.subjectDeficiência de Proteína Cpt_PT
dc.titleFamilial thrombotic risk based on the genetic background of Protein C Deficiency in a Portuguese Studypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage307pt_PT
oaire.citation.issue4pt_PT
oaire.citation.startPage294-307pt_PT
oaire.citation.volume95pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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