title: Antithrombin cambridge II (Ala384Ser): clinical, functional and haplotype analysis of 18 families.
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.
authors.affiliation: Department of Haematology, Royal Free Hospital and School of Medicine, London, UK. djp@rfhsm.ac.uk
authors.forename: D J
authors.initials: DJ
authors.lastname: Perry
authors.forename: M E
authors.initials: ME
authors.lastname: Daly
authors.forename: R C
authors.initials: RC
authors.lastname: Tait
authors.forename: I D
authors.initials: ID
authors.lastname: Walker
authors.forename: K
authors.initials: K
authors.lastname: Brown
authors.forename: N J
authors.initials: NJ
authors.lastname: Beauchamp
authors.forename: F E
authors.initials: FE
authors.lastname: Preston
authors.forename: H
authors.initials: H
authors.lastname: Gyde
authors.forename: P L
authors.initials: PL
authors.lastname: Harper
authors.forename: R W
authors.initials: RW
authors.lastname: Carrell
mesh_terms: D000409:Alanine / Q000235:genetics; D000990:Antithrombin III / Q000235:genetics*; D020152:Antithrombin III Deficiency; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012694:Serine / Q000235:genetics; D013923:Thromboembolism / Q000235:genetics*
chemical_list: D012694:Serine; D000990:Antithrombin III; D000409:Alanine