Two novel fibrinogen variants found in patients with pulmonary embolism and their families

Abstract

Background: The occurrence of dysfibrinogen is quite rare in comparison with other hemostatic defects, specially in cases of venous thrombosis. Objectives: Fibrinogen is known to have multiple functions, which are not evaluated by simple coagulation testing.We have used gel electrophoresis to search for new mutations. Patients and methods: Specimens of purified fibrinogen from 217 consecutive patients with familial or recurrent or early thrombosis and from 490 control subjects were evaluated by electrophoresis. Plasma fibrinogen levels and coagulation-dependent tests (electromechanical and optical coagulometric determinations, immunological measurement, thrombinandReptilase1times)werenormal.Results: Twonovel familial variants were detected. For a 42-year-old patient, an inframe 117 base pair insertion in theAa-chaingene caused a 5-kDa mobility shift of theAachain.This corresponds to a 39 amino acid duplication in the connector domain (fibrinogen Champagne au Montd'Or).Thispatternwasalsofoundinthepatient'smotherand child.Asecond 31-year-old patient presented an extra band under non-reducingconditions,30 kDa larger thanHMWfibrinogenand reacting with antifibrinogen antibodies (fibrinogen Lozanne). A heterozygous 5909A!G mutation was found on the Bb-chain gene leading to heterozygous Bb Tyr236! stop codon. The predicted truncated Bb chain could participate in chain assembly. Twofamilymemberswerealsoaffected,oneofwhomhadsuffered earlyvenous thrombosis.Conclusions: Electrophoretic testing of apparently normal fibrinogens can reveal newvariantswhichmay be clinically relevant. © 2003 International Society on Thrombosis and Haemostasis.