γD318Y fibrinogen shows no fibrin polymerization due to defective "A-a" and "B-b" interactions, whereas that of γK321E fibrinogen is nearly normal

ArticleThrombosis research. 182: 150-158. (2019)journal articl

Fibrin monomers derived from thrombogenic dysfibrinogenemia, Naples-type variant (BβAla68Thr), showed almost entirely normal polymerization

ArticleTHROMBOSIS RESEARCH.172:1-3(2018)journal articl

A novel variant fibrinogen, AαE11del, demonstrating the importance of AαE11 residue in thrombin binding

ArticleInternational journal of hematology. 114(5): 591-598. (2021)journal articl

Recombinant γY278H Fibrinogen Showed Normal Secretion from CHO Cells, but a Corresponding Heterozygous Patient Showed Hypofibrinogenemia

ArticleInternational journal of molecular sciences. 22(10): 5218(2021)journal articl

Heterozygous Variant Fibrinogen γA289V (Kanazawa III) Was Confirmed as Hypodysfibrinogenemia by Plasma and Recombinant Fibrinogens

Introduction: Congenital fibrinogen disorders are classified as afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, and hypodysfibrinogenemia. However, difficulties are associated with discriminating between dysfibrinogenemia, hypofibrinogenemia, and hypodysfibrinogenemia using routine analyses. We previously reported a heterozygous variant fibrinogen (γA289V; Kanazawa III) as hypodysfibrinogenemia; however, the same variant had previously been described as hypofibrinogenemia. To clarify the production of γA289V fibrinogen, we expressed recombinant γA289V (r-γA289V) fibrinogen and compared it with wild-type (WT) and adjacent recombinant variant fibrinogens. Methods: Target mutations were introduced into a fibrinogen γ-chain expression vector by site-directed mutagenesis, and the vector was then transfected into Chinese hamster ovary cells to produce recombinant fibrinogen. Fibrinogen was purified from the plasma of the proposita, and culture media and fibrinogen functions were analyzed using fibrin polymerization, plasmin protection, and FXIIIa-catalyzed fibrinogen cross-linking. Results: The fibrinogen concentration ratio of the culture media to cell lysates was markedly lower for r-γA289V fibrinogen than for WT. Because the secretion of recombinant γF290L (r-γF290L) fibrinogen was similar to WT, we compared r-γF290L fibrinogen functions with WT. The fibrin polymerization of Kanazawa III plasma (K-III) fibrinogen was significantly weaker than normal plasma fibrinogen. Moreover, K-III fibrinogen showed a markedly reduced “D:D” interaction. However, all functions of r-γF290L fibrinogen were similar to WT. An in silico analysis confirmed the above results. Conclusion: The present results demonstrated that γA289 is crucial for the γ-module structure, and the γA289V substitution markedly reduced fibrinogen secretion. Moreover, K-III fibrinogen showed markedly reduced fibrin polymerization and “D:D” interactions. γA289V fibrinogen was confirmed as hypodysfibrinogenemia.ArticleINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY.42(2):190-197(2020)journal articl

A Novel Amino Acid Substitution, Fibrinogen Bβp.Pro234Leu, Associated with Hypofibrinogenemia Causing Impairment of Fibrinogen Assembly and Secretion

ArticleInternational journal of molecular sciences. 21(24): 9422(2020)journal articl

Novel variant fibrinogen γp.C352R produced hypodysfibrinogenemia leading to a bleeding episode and failure of infertility treatment

ArticleInternational journal of hematology. 114(3): 325-333. (2021)journal articl

Acquired dysfibrinogenemia: monoclonal λ-type IgA binding to fibrinogen caused lower functional plasma fibrinogen level and abnormal clot formation

ArticleInternational journal of hematology. 112(1): 96-104. (2020)journal articl

Screening method for congenital dysfibrinogenemia using clot waveform analysis with the Clauss method

ArticleInternational journal of laboratory hematology. 43(2): 281-289(2021)journal articl

Automated screening procedure for the phenotypes of congenital fibrinogen disorders using novel parameters, |min1|c and Ac/|min1|c, obtained from clot waveform analysis using the Clauss method

ArticleClinica chimica acta. 521: 170-176(2021)journal articl