A novel variant fibrinogen, deletion of Bβ111Ser in coiled-coil region, affecting fibrin lateral aggregation

Abstract

Background Functional fibrinogen concentration of a male infant showed < 0.50 g/l and we speculated this patient as a dysfibrinogenemia or hypofibrinogenemia. Methods We analyzed propositus and his parent by DNA sequencing and by thrombin-catalyzed fibrin polymerization for purified plasma fibrinogen. Results Although functional fibrinogen determinations based on Clauss method showed the marked discrepancy of values among 3 sets of reagent and analyzer, we found a novel heterozygous variant fibrinogen, Kyoto IV, caused by 3-bp deletion in Bβ-chain gene corresponding to the deletion of 111Ser located in coiled-coil region. We suggested that the discrepancy of fibrinogen values among 3 assays was caused by the difference in NaCl concentration in reagents for determination and analyzed the polymerization under the conditions of various NaCl concentrations. Although under normal physiological conditions Kyoto IV fibrinogen augmented the polymerization as compared with normal control, in 0.21 mol/l NaCl Kyoto IV fibrinogen showed abruptly impaired polymerization curve compared with normal control. Conclusion Variant fibrinogen, BβΔ111Ser, showed augmented lateral aggregation under normal physiological conditions and the residue located in coiled-coil region, Bβ111Ser, plays an important role in the lateral aggregation.