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Thromb Haemost 1998; 79(02): 249-253
DOI: 10.1055/s-0037-1614973
DOI: 10.1055/s-0037-1614973
Letters to the Editor
Antithrombin Cambridge II (Ala384Ser): Clinical, Functional and Haplotype Analysis of 18 Families
The financial support of the Wellcome Trust, The British Heart Foundation and Medical Research Council is gratefully acknowledged. DJP is supported by the Katharine Dormandy Trust for Haemophilia and Allied Disorders.
Weitere Informationen
Publikationsverlauf
Received
27. Juni 1996
Accepted after resubmission
16. September 1997
Publikationsdatum:
08. Dezember 2017 (online)
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.
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