title: Novel point mutation in fibrinogen (Innsbruck; BβArg44Gly). Phenotypic differences compared to another mutation (fibrinogen Nijmegen) at the same position.
abstract: This is a report of a novel fibrinogen point mutation (fibrinogen Innsbruck), a C/G point mutation at position 220 of exon two of the fibrinogen Bβ-chain leading to BβArg44Gly. The heterozygous mutation was found in a 16-year-old adolescent, hospitalized for the management of juvenile depression, who suffered from multiple epistaxis episodes during his stay at the university hospital in Innsbruck, Austria. Fibrinogen (based on the Clauss method) and fibrinogen antigen levels were highly discrepant (86 vs. 223 mg/dl) with thrombin time and reptilase time being in the respective upper reference ranges. Densitometric analysis of electrophoretic band pattern showed a reduction of α-polymers, indicating an impaired fibrin polymerization. This is in agreement with structural analysis, which showed a disturbance of the flexibility and structure of the region surrounding the fibrinoeptide B cleavage site. Fibrinogen Nijmegen, a mutation at the same position, is causative for thrombosis, whereas fibrinogen Innsbruck appears to lead to a bleeding tendency, illustrating that even mutations at the same position can cause contrary symptoms.
authors.affiliation: Dr. Philipp Würtinger, Institute of Medical and Chemical Laboratory Diagnostics (ZIMCL), Medical University of Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria, Tel. +43/512/50 48 20 03; Fax +43/05 12/50 42 40 88, E-mail: philipp.wuertinger@uki.at.
authors.forename: P
authors.initials: P
authors.lastname: Würtinger
authors.forename: A
authors.initials: A
authors.lastname: Griesmacher
authors.forename: V
authors.initials: V
authors.lastname: Ivaškevičius
authors.forename: A
authors.initials: A
authors.lastname: Biswas
authors.forename: S
authors.initials: S
authors.lastname: Zehetbauer
authors.forename: J
authors.initials: J
authors.lastname: Oldenburg
authors.forename: K
authors.initials: K
authors.lastname: Hohenstein
authors.forename: G
authors.initials: G
authors.lastname: Weigel
mesh_terms: D000293:Adolescent; D005260:Female; D005340:Fibrinogen / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006470:Hemorrhage / Q000097:blood / Q000175:diagnosis* / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D005340:Fibrinogen
keywords: Fibrinogen; congenital dysfibrinogenemia; fibrinogen mutation