title: Homozygous truncation of the fibrinogen A alpha chain within the coiled coil causes congenital afibrinogenemia.
abstract: The molecular basis of a novel congenital afibrinogenemia has been determined. The proposita, the only affected member in a consanguineous Norwegian family, suffers from a moderate to severe bleeding disorder due to the total absence of any detectable fibrinogen. Dot blots of solubilized platelets revealed a small amount of gamma chain but no A alpha or B beta chains, whereas no chains were detected in plasma dot blots. DNA sequencing of the A alpha chain gene revealed a homozygous C-->T transversion 557 nucleotides from the transcription initiation site. This nucleotide change predicts the nonsense mutation A alpha 149 Arg (CGA)-->stop (TGA). Early truncation of the A alpha chain appears to result in defective assembly or secretion of fibrinogen, probably due to the removal of the C-terminal disulfide ring residues that are critically required for the formation of a stable 3-chained half molecule. (Blood. 2000;96:773-775)
authors.affiliation: Molecular Pathology Laboratory, Canterbury Health Laboratories, Christchurch, New Zealand. andrew.fellowes@chmeds.ac.nz
authors.forename: A P
authors.initials: AP
authors.lastname: Fellowes
authors.forename: S O
authors.initials: SO
authors.lastname: Brennan
authors.forename: R
authors.initials: R
authors.lastname: Holme
authors.forename: H
authors.initials: H
authors.lastname: Stormorken
authors.forename: F R
authors.initials: FR
authors.lastname: Brosstad
authors.forename: P M
authors.initials: PM
authors.lastname: George
mesh_terms: D000328:Adult; D000347:Afibrinogenemia / Q000150:complications / Q000188:drug therapy / Q000235:genetics*; D005169:Factor VIII / Q000627:therapeutic use; D005260:Female; D005340:Fibrinogen / Q000032:analysis / Q000737:chemistry* / Q000235:genetics* / Q000627:therapeutic use; D006470:Hemorrhage / Q000209:etiology; D006720:Homozygote; D006801:Humans; D009154:Mutation; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014841:von Willebrand Factor / Q000627:therapeutic use
chemical_list: D014841:von Willebrand Factor; D005169:Factor VIII; D005340:Fibrinogen