What is it about?
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. 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
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Why is it important?
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.
Perspectives
This study, although geographically limited, illustrates the advantages of identifying the most prevalent mutations in a region. In conclusion, we demonstrated in this study the importance of establishing the familial thrombotic risk based on the genetic background. Familial mutations, in association with PROC haplotypes, correlated strongly with PC levels as well as the thrombotic episode number and age of onset.
Dr Teresa Fidalgo
Read the Original
This page is a summary of: Familial thrombotic risk based on the genetic background of Protein C Deficiency in a Portuguese Study, European Journal Of Haematology, March 2015, Wiley,
DOI: 10.1111/ejh.12488.
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