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.
Methods and Results. We screened the gene by conformation sensitive gel electrophoresis and sequenced the
mismatched regions using fluorescend 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.
Key words:
antithrombin, mutation, gene, thrombosis, heparin.
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