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, thrombin and Reptilase(R) times) were normal. RESULTS: Two novel familial variants were detected. For a 42-year-old patient, an in-frame 117 base pair insertion in the Aalpha-chain gene caused a 5-kDa mobility shift of the Aalpha chain. This corresponds to a 39 amino acid duplication in the connector domain (fibrinogen Champagne au Mont d'Or). This pattern was also found in the patient's mother and child. A second 31-year-old patient presented an extra band under non-reducing conditions, 30 kDa larger than HMW fibrinogen and reacting with antifibrinogen antibodies (fibrinogen Lozanne). A heterozygous 5909A-->G mutation was found on the Bbeta-chain gene leading to heterozygous Bbeta Tyr236--> stop codon. The predicted truncated Bbeta chain could participate in chain assembly. Two family members were also affected, one of whom had suffered early venous thrombosis. CONCLUSIONS: Electrophoretic testing of apparently normal fibrinogens can reveal new variants which may be clinically relevant.
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, thrombin and Reptilase(R) times) were normal. RESULTS: Two novel familial variants were detected. For a 42-year-old patient, an in-frame 117 base pair insertion in the Aalpha-chain gene caused a 5-kDa mobility shift of the Aalpha chain. This corresponds to a 39 amino acid duplication in the connector domain (fibrinogen Champagne au Mont d'Or). This pattern was also found in the patient's mother and child. A second 31-year-old patient presented an extra band under non-reducing conditions, 30 kDa larger than HMW fibrinogen and reacting with antifibrinogen antibodies (fibrinogenLozanne). A heterozygous 5909A-->G mutation was found on the Bbeta-chain gene leading to heterozygous BbetaTyr236--> stop codon. The predicted truncated Bbeta chain could participate in chain assembly. Two family members were also affected, one of whom had suffered early venous thrombosis. CONCLUSIONS: Electrophoretic testing of apparently normal fibrinogens can reveal new variants which may be clinically relevant.
Authors: Roman Kotlín; Zuzana Reicheltová; Jirí Suttnar; Peter Salaj; Ingrid Hrachovinová; Tomás Riedel; Martin Malý; Milan Oravec; Jan Kvasnicka; Jan Evangelista Dyr Journal: J Thromb Thrombolysis Date: 2010-10 Impact factor: 2.300
Authors: Monika Brunclikova; Tomas Simurda; Jana Zolkova; Miroslava Sterankova; Ingrid Skornova; Miroslava Dobrotova; Zuzana Kolkova; Dusan Loderer; Marian Grendar; Jan Hudecek; Jan Stasko; Peter Kubisz Journal: J Clin Med Date: 2022-02-18 Impact factor: 4.241