Antithrombin cambridge II (Ala384Ser): clinical, functional and haplotype analysis of 18 families

Perry, D.J., Daly, M.E., Tait, R.C. , Walker, I.D., Brown, K., Beauchamp, N.J., Preston, F.E., Gyde, H., Harper, P.L. and Carrell, R.W. (1998) Antithrombin cambridge II (Ala384Ser): clinical, functional and haplotype analysis of 18 families. Thrombosis and Haemostasis, 79(2), pp. 239-253. (doi: 10.1055/s-0037-1614973) (PMID:9493570)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Walker, Prof Isobel and Tait, Dr Robert
• Authors: Perry, D.J., Daly, M.E., Tait, R.C., Walker, I.D., Brown, K., Beauchamp, N.J., Preston, F.E., Gyde, H., Harper, P.L., and Carrell, R.W.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Thrombosis and Haemostasis
• Publisher: Georg Thieme
• ISSN: 0340-6245
• ISSN (Online): 2567-689X