title: Antithrombin-Gly 424 Arg: a novel point mutation responsible for type 1 antithrombin deficiency and neonatal thrombosis.
abstract: Inherited type 1 antithrombin (AT) III deficiency is characterized by a decrease of immunoreactive and functional protein levels to about 50%. The disorder is associated with a significantly increased risk of thromboembolism. We have investigated the molecular basis of type 1 AT deficiency in a Belgian family. The diagnosis of the disease was primarily made in a newborn girl with unusually severe thrombotic complications. Using the polymerase chain reaction and single-strand conformation polymorphism analysis, followed by direct sequencing of AT gene fragments, we identified a novel point mutation in exon 6. We detected a G to C substitution in the first position of codon 424 leading to a glycine to arginine substitution. The modification at this highly conserved position in the serine protease inhibitor gene family probably leads to an unstable mutant-gene product. The mutation creates a unique restriction site for the enzyme Hha I in exon 6. This change permitted a rapid and accurate screening of the kindred with identification of the molecular defect in five other family members.
authors.affiliation: Department of Hematology, Academic Hospital of the Free University of Brussels, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Jochmans
authors.forename: W
authors.initials: W
authors.lastname: Lissens
authors.forename: R
authors.initials: R
authors.lastname: Vervoort
authors.forename: S
authors.initials: S
authors.lastname: Peeters
authors.forename: M
authors.initials: M
authors.lastname: De Waele
authors.forename: I
authors.initials: I
authors.lastname: Liebaers
mesh_terms: D000328:Adult; D000990:Antithrombin III / Q000235:genetics; D020152:Antithrombin III Deficiency; D001120:Arginine; D001483:Base Sequence; D004247:DNA / Q000737:chemistry; D005260:Female; D005998:Glycine; D006801:Humans; D007231:Infant, Newborn; D008969:Molecular Sequence Data; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D013927:Thrombosis / Q000209:etiology*
chemical_list: D000990:Antithrombin III; D004247:DNA; D001120:Arginine; D005998:Glycine