Summary
Thirty-one individuals from 18 unrelated families with antithrombin deficiency have
been identified as having a single point mutation within codon 384 (13268 GCA→TCA)
resulting in an alanine to serine substitution. Six families (11 individuals) were
identified by the screening of individuals with thromboembolic disease or with a family
history of thromboembolic disease, whilst the remaining 12 families (20 individuals)
were identified by screening of asymptomatic blood donors. Four individuals had a
history of venous thrombotic disease, a further 2 gave a history of superficial thrombophlebitis
but the remaining 25 individuals were asymptomatic. Affected individuals demonstrated
normal immunological levels of antithrombin but a decrease in anti-IIa activity in
the presence of heparin. Haplotype analysis was used to examine the possibility of
a founder effect to explain the high frequency of this non-CpG mutation. 29/31 individuals
showed a single common “core” haplotype, the only variation existing in the number
of copies of an (ATT)n repeat polymorphism – 13, 14, 15 or 17. The results suggest
that at most there are four independent origins for this mutation.
