title: [Molecular basis of hereditary antithrombin defects in 10 Czech families].
abstract: BACKGROUND
  Molecular basis of antithrombin deficiency has not yet been studied in Czech Republic. We looked for the causal mutations throughout the antithrombin gene in 26 patients from 10 unrelated families with antithrombin defect.
  
  
  RESULTS
  We screened the gene by conformation sensitive gel electrophoresis and sequenced the mismatched regions using fluorescence technology to characterise mutations and polymorphisms. Mutations were detected in all ten families. Four novel mutations were identified in four families with type I antithrombin defect: Trp-6Arg, 5386-5387delCT, Glu163Stop, and 13246-13248del TGA causing deletion of Glu377 with change of Asn376 to Lys. In other three type I families we found following mutations: splicing site mutation G2777C, Arg197Stop and entire gene deletion. In the family carrying Trp-6Arg mutation antithrombin Vienna (Gln118Pro) was also detected. Leu99Phe recurrent in south-eastern Europe was identified in three families with type II defect. Only the homozygous carries of the mutation were symptomatic, although the heterozygous carries had decreased functional levels.
  
  
  CONCLUSIONS
  Four novel mutations in families with type I antithrombin deficiency were characterised. In one family two different genetic defects were identified to be responsible for type I and II phenotypes. Altogether our data agree with the expected heterogeneity of the AT genetic defect.
authors.affiliation: Ustav hematologie a krevní transfuze, Praha.
authors.forename: I
authors.initials: I
authors.lastname: Hrachovinová
authors.forename: D
authors.initials: D
authors.lastname: Habart
authors.forename: P
authors.initials: P
authors.lastname: Salaj
authors.forename: M
authors.initials: M
authors.lastname: Matysková
authors.forename: Z
authors.initials: Z
authors.lastname: Vorlová
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D005337:Fibrin / Q000172:deficiency* / Q000235:genetics*; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011655:Pulmonary Embolism / Q000235:genetics; D013927:Thrombosis / Q000235:genetics
chemical_list: D005337:Fibrin
vernacular_title: Molekulární podstata vrozeného defektu antitrombinu u deseti ceských rodin.