title: A novel fibrinogen Bbeta chain frameshift mutation in a patient with severe congenital hypofibrinogenaemia.
abstract: 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 Aalpha chain. In this study, we identified a genetic defect in the fibrinogen Bbeta-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 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 GGGG-->GGG mutation at nucleotide 7,969-7,972 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 Bbeta-chain is 27 amino acids shorter than the normal Bbeta-chain and a central beta-strand in the globular betaC domain is absent, which may lead to destabilization of the entire beta-domain. To the best of our knowledge, this is the first report of such a mutation which is associated with severe hypofibrinogenemia.
authors.affiliation: The Center Laboratory of Anhui Provincial Hospital, the Second Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Xiucai
authors.initials: X
authors.lastname: Xu
authors.forename: Jingsheng
authors.initials: J
authors.lastname: Wu
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Zhai
authors.forename: Rongfu
authors.initials: R
authors.lastname: Zhou
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.forename: Hongli
authors.initials: H
authors.lastname: Wang
authors.forename: Kaiyang
authors.initials: K
authors.lastname: Ding
authors.forename: Zimin
authors.initials: Z
authors.lastname: Sun
authors.forename: Heyu
authors.initials: H
authors.lastname: Ni
mesh_terms: D000328:Adult; D000347:Afibrinogenemia / Q000097:blood / Q000235:genetics*; D001777:Blood Coagulation; D002681:China; D004252:DNA Mutational Analysis; D005340:Fibrinogen / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D016368:Frameshift Mutation; D006801:Humans; D008297:Male; D008958:Models, Molecular; D010314:Partial Thromboplastin Time; D011487:Protein Conformation; D013918:Thrombin Time
chemical_list: C115499:BBeta fibrinogen; D005340:Fibrinogen