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

• Published in: British journal of haematology 2000-09, Vol.110 (3), p.731-734
• Main Authors: Picard, Véronique, Bura, Alessandra, Emmerich, Joseph, Alhenc‐Gelas, Martine, Biron, Christine, Houbouyan‐Reveillard, Lucie L., Molho, Pascale, Labatide‐Alanore, Agnès, Sié, Pierre, Toulon, Pierre, Verdy, Elisabeth, Aiach, Martine
• Format: Article
• Language: English
• Subjects: antithrombin; Antithrombin III Deficiency - genetics; Binding Sites - genetics; Biological and medical sciences; Exons; Fibrin - deficiency; Fibrin - genetics; gene; Gene Deletion; Hematologic and hematopoietic diseases; Hematology; Heterozygote; Humans; Medical sciences; mutation; Mutation, Missense; Platelet diseases and coagulopathies; Polymerase Chain Reaction; serpin; thrombosis; Thrombosis - genetics
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2000.02245.x

We have investigated the molecular bases of familial antithrombin deficiency in eight French families. Eight mutations in the antithrombin coding exons were identified, seven of which were novel mutations. In all cases, individuals were heterozygous for the mutation. We found two small frameshift deletions in exon 3a, leading to type I deficiency. Five missense mutations in exons 3b or 5 also caused type I deficiency and their potential consequences on the antithrombin three‐dimensional structure were analysed. The last mutation in exon 4 was associated with a type II ‘reactive site’ deficiency: a dysfunctional antithrombin that is affected in its interaction with thrombin was present in circulation.