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Deutsches Institut für Urbanistik
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Xiucai Xu, Jingsheng Wu, Zhimin Zhai, Rongfu Zhou, Xuefeng Wang, Hongli Wang, Kaiyang Ding, Zimin Sun, Heyu Ni

A novel fibrinogen B chain frameshift mutation in a patient with severe congenital hypofibrinogenaemia

Keywords: Congenital hypofibrinogenemia / afibrinogenemia, fibrinogen/fibrin, gene mutation, platelet aggregation

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 A chain. In this study, we identified a genetic defect in the fibrinogen B-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 (1.71.8 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 propositus could not be detected by western blotting, and his platelet aggregation was severely impaired. DNA screening of the whole fibrinogen gene revealed a homozygous GGGGGGG mutation at nucleotide 79697972 in his FGB gene. The propositus parents are both heterozygous for this mutation. This mutation contributes to Gly419Val, and the 419434 codons are frame shifted, and a stop codon is formed at codon 435. The predicted truncated B-chain is 27 amino acids shorter than the normal B-chain and a central -strand in the globular C domain is absent, which may lead to destabilization of the entire -domain. To the best of our knowledge, this is the first report of such a mutation which is associated with severe hypofibrinogenemia.

Thrombosis and Haemostasis, Schattauer

Print ISSN: 0340-6245
Volume: 95, 06/2006
Pages: 931 - 935

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