Summary

Congenital afibrinogenemia and severe hypofibrinogenemia are severe bleeding disorders characterized by either undetectable or very low levels of fibrinogen in patients’ plasma and platelets. A majority of the reported cases are caused by mutations in the fibrinogen Aα chain. In this study, we identified a genetic defect in the fibrinogen Bβ -chain ( FGB) underlying severe hypofibrinogenemia. The propositus frequently displayed bleeding episodes with a prolonged blood-clotting time (thrombin time > 180 s,activated partial thromboplastin time > 300 s, prothrombin time > 120 s) and had a very low level of plasma fibrinogen (1.7–1.8 mg/dl). His parents had a consanguineous marriage, and their functional and immunological fibrinogen was approximately half of the normal level.The platelet fibrinogen level of the proposi- tus could not be detected by western blotting, and his platelet aggregation was severely impaired. DNA screening of the whole fibrinogen gene revealed a homozygous GGGG → GGG mutation at nucleotide 7969–7972 in his FGB gene.The propositus’ parents are both heterozygous for this mutation.This mutation contributes to Gly419→ Val, and the 419–434 codons are frame shifted, and a stop codon is formed at codon 435.The predicted truncated Bβ -chain is 27 amino acids shorter than the normal B β -chain and a central β -strand in the globular β C domain is absent, which may lead to destabilization of the entire β -domain.To the best of our knowledge, this is the first report of such a mutation which is associated with severe hypofibrinogenemia.