Familial thrombotic risk based on the genetic background of Protein C Deficiency in a Portuguese Study.
Eur J Haematol
; 95(4): 294-307, 2015 Oct.
Article
in En
| MEDLINE
| ID: mdl-25533856
ABSTRACT
INTRODUCTION:
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 ANDMETHODS:
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thrombosis
/
Protein C
/
Protein C Deficiency
/
Genetic Predisposition to Disease
/
Genetic Association Studies
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
En
Journal:
Eur J Haematol
Journal subject:
HEMATOLOGIA
Year:
2015
Document type:
Article
Affiliation country: