title: Molecular bases of antithrombin deficiency in French families: identification of seven novel mutations in the antithrombin gene.
abstract: 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.
authors.affiliation: Service d'Hématologie Biologique, Hôpital Broussais, and Unité INSERM 428, UFR de Pharmacie, Université Paris V, France. vzpicard@yahoo.fr
authors.forename: V
authors.initials: V
authors.lastname: Picard
authors.forename: A
authors.initials: A
authors.lastname: Bura
authors.forename: J
authors.initials: J
authors.lastname: Emmerich
authors.forename: M
authors.initials: M
authors.lastname: Alhenc-Gelas
authors.forename: C
authors.initials: C
authors.lastname: Biron
authors.forename: L L
authors.initials: LL
authors.lastname: Houbouyan-Reveillard
authors.forename: P
authors.initials: P
authors.lastname: Molho
authors.forename: A
authors.initials: A
authors.lastname: Labatide-Alanore
authors.forename: P
authors.initials: P
authors.lastname: Sié
authors.forename: P
authors.initials: P
authors.lastname: Toulon
authors.forename: E
authors.initials: E
authors.lastname: Verdy
authors.forename: M
authors.initials: M
authors.lastname: Aiach
mesh_terms: D020152:Antithrombin III Deficiency / Q000235:genetics*; D001665:Binding Sites / Q000235:genetics; D005091:Exons; D005337:Fibrin / Q000172:deficiency* / Q000235:genetics; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D013927:Thrombosis / Q000235:genetics*
chemical_list: D005337:Fibrin