Molecular bases of antithrombin deficiency in French families: identification of seven novel mutations in the antithrombin gene

We have investigated the molecular bases of familial antithrombin deficienc y in eight French families, Eight mutations in the antithrombin coding exon s were identified, seven of which were novel mutations. In all cases, indiv iduals were heterozygous for the mutation. We found two small frameshift de letions in exon 3a, leading to type I deficiency. Five missense mutations i n exons 3b or 5 also caused type I deficiency and their potential consequen ces on the antithrombin three-dimensional structure were analysed. The last mutation in exon 4 was associated with a type II 'reactive site' deficienc y: a dysfunctional antithrombin that is affected in its interaction with th rombin was present in circulation.