Founder effect is responsible for the p.Leu131Phe heparin-binding-site antithrombin mutation common in Hungary; phenotype analysis in a large cohort. - PubMed - NCBI
Founder effect is responsible for the p.Leu131Phe heparin-binding-site antithrombin mutation common in Hungary; phenotype analysis in a large cohort.
Gindele R1,
Oláh Z2,
Ilonczai P2,
Speker M1,
Udvari Á1,
Selmeczi A1,
Pfliegler G3,
Marján E4,
Kovács B1,
Boda Z2,
Muszbek L1,5,
Bereczky Z1.
Abstract
BACKGROUND:
Antithrombin (AT) is a key regulator of the coagulation. In type II deficiency the heparin-binding site defect (type II HBS) is considered as relatively low thrombosis risk. OBJECTIVES:
Our aims were to search for SERPINC1 mutation(s) and to describe the clinical and laboratory phenotype of a large number of AT Budapest3 (ATBp3, p.Leu131Phe) carriers and confirm the presence of a founder effect PATIENTS/METHODS: AT deficient patients were recruited and carriers of ATBp3, n=102 (63 families) were selected. To investigate the founder effect 8 intragenic SNP's, a 5'-length dimorphism and 5 microsatellite markers were detected. Clinical and laboratory data of the patients were collected and analyzed RESULTS: In AT deficiency 16 different causative mutations were found and the great majority of patients were of type II HBS subtype. Most of them (n=102/118, 86.5%) carried the ATBp3 mutation. The ATBp3 mutant allele was associated with one single haplotype, while different haplotypes were detected in the case of normal allele. The anti-FXa based AT activity assay that we used, could detect all ATBp3 patients with high sensitivity in our cohort. ATBp3 homozygosity (n=26) was associated with thrombosis at very young age and conferred a high thrombotic risk. Half of the heterozygotes (n=41/76, 53.9%) also suffered from venous and/or arterial thrombosis and pregnancy complications were also recorded CONCLUSION: In Hungary, the founder mutation, ATBp3 is the most common AT deficiency. Our study is the first where the clinical characterization of ATBp3 mutation was executed in a large population. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
- PMID:
- 26748602
- [PubMed - as supplied by publisher]
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