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Hamostaseologie 2023; 43(06): 426-431
DOI: 10.1055/a-2116-8957
Original Article

A Novel Fibrinogen Mutation p.BβAla68Asp Causes an Inherited Dysfibrinogenemia

Kaiqi Jia
1   Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
2   Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, Zhejiang, People's Republic of China
,
Manlin Zeng
1   Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
,
Xiaoyong Zheng
1   Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
,
Haixiao Xie
1   Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
,
Lihong Yang
1   Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
,
Yaosheng Xie
1   Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
,
Mingshan Wang
1   Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
2   Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province, Wenzhou, Zhejiang, People's Republic of China
› Author Affiliations Funding This work was funded by the Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province (2022E10022) and the Science and Technology Plan Fund of Wenzhou (Y20220746).
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Erratum: A Novel Fibrinogen Mutation p.BβAla68Asp Causes an Inherited DysfibrinogenemiaHamostaseologie 2023; 43(06): e1-e1
DOI: 10.1055/a-2218-6919

Abstract

Objective Our study aimed to analyze the phenotype and genotype of a pedigree with inherited dysfibrinogenemia, and preliminarily elucidate the probable pathogenesis.

Methods The one-stage clotting method was used to test the fibrinogen activity (FIB:C), whereas immunoturbidimetry was performed to quantify the fibrinogen antigen (FIB:Ag). Furthermore, DNA sequence analysis was conducted to confirm the site of mutation. Conservation analysis and protein model analysis were performed using online bioinformatics software.

Results The FIB:C and FIB:Ag of the proband were 1.28 and 2.20 g/L, respectively. Gene analysis revealed a heterozygous c.293C > A (p.BβAla68Asp) mutation in FGB. Bioinformatics and modeling analysis suggested that the missense mutation could potentially have a deleterious effect on fibrinogen.

Conclusion The BβAla68Asp mutation in exon 2 of FGB may account for the reduced FIB:C levels observed in the pedigree. To our knowledge, this point mutation is the first report in the world.

Keywords

FGB - novel mutation - dysfibrinogenemia - genetic analysis

Ethical Approval

Our study was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University (China).




Publication History

Received: 04 April 2023

Accepted: 20 June 2023

Article published online:
29 July 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Luo S, Xu Q, Xie Y. et al. A novel heterozygous mutation (γIIe367Thr) causes congenital dysfibrinogenemia in a Chinese family. Blood Coagul Fibrinolysis 2020; 31 (08) 569-574
    CrossrefPubMedSearch in Google Scholar
  • 2 Li S, Wang M, Li X. et al. Analysis of an inherited dysfibrinogenemia pedigree associated with a heterozygous mutation in the FGA gene. Hamostaseologie 2020; 40 (05) 642-648
    Thieme ConnectPubMedSearch in Google Scholar
  • 3 Tiscia GL, Margaglione M. Human fibrinogen: molecular and genetic aspects of congenital disorders. Int J Mol Sci 2018; 19 (06) 19
    CrossrefPubMedSearch in Google Scholar
  • 4 Tajdar M, Orlando C, Casini A. et al. Heterozygous FGA p.Asp473Ter (fibrinogen Nieuwegein) presenting as antepartum cerebral thrombosis. Thromb Res 2018; 163: 185-189
    CrossrefPubMedSearch in Google Scholar
  • 5 Chapin JC, Hajjar KA. Fibrinolysis and the control of blood coagulation. Blood Rev 2015; 29 (01) 17-24
    CrossrefPubMedSearch in Google Scholar
  • 6 Casini A, de Moerloose P, Neerman-Arbez M. Clinical features and management of congenital fibrinogen deficiencies. Semin Thromb Hemost 2016; 42 (04) 366-374
    Search in Google Scholar
  • 7 Casini A, Neerman-Arbez M, Ariëns RA, de Moerloose P. Dysfibrinogenemia: from molecular anomalies to clinical manifestations and management. J Thromb Haemost 2015; 13 (06) 909-919
    CrossrefPubMedSearch in Google Scholar
  • 8 Kamijo T, Nagata K, Taira C, Higuchi Y, Arai S, Okumura N. Fibrin monomers derived from thrombogenic dysfibrinogenemia, Naples-type variant (BβAla68Thr), showed almost entirely normal polymerization. Thromb Res 2018; 172: 1-3
    CrossrefPubMedSearch in Google Scholar
  • 9 Undas A, Casini A. Congenital structural and functional fibrinogen disorders: a primer for internists. Pol Arch Intern Med 2019; 129 (12) 913-920
    PubMedSearch in Google Scholar
  • 10 Casini A, Blondon M, Lebreton A. et al. Natural history of patients with congenital dysfibrinogenemia. Blood 2015; 125 (03) 553-561
    Search in Google Scholar
  • 11 Acharya SS, Dimichele DM. Rare inherited disorders of fibrinogen. Haemophilia 2008; 14 (06) 1151-1158
    CrossrefPubMedSearch in Google Scholar
  • 12 Al-Mondhiry H, Bilezikian SB, Nossel HL. Fibrinogen “New York” – an abnormal fibrinogen associated with thromboembolism: functional evaluation. Blood 1975; 45 (05) 607-619
    CrossrefPubMedSearch in Google Scholar
  • 13 Meh DA, Mosesson MW, Siebenlist KR. et al. Fibrinogen Naples I (B beta A68T) nonsubstrate thrombin-binding capacities. Thromb Res 2001; 103 (01) 63-73
    CrossrefPubMedSearch in Google Scholar
  • 14 Casini A, Lukowski S, Quintard VL. et al. FGB mutations leading to congenital quantitative fibrinogen deficiencies: an update and report of four novel mutations. Thromb Res 2014; 133 (05) 868-874
    CrossrefPubMedSearch in Google Scholar
  • 15 Ceznerová E, Kaufmanová J, Sovová Ž. et al. Structural and functional characterization of four novel fibrinogen mutations in FGB causing congenital fibrinogen disorder. Int J Mol Sci 2022; 23 (02) 23
    Search in Google Scholar
  • 16 Koopman J, Haverkate F, Lord ST, Grimbergen J, Mannucci PM. Molecular basis of fibrinogen Naples associated with defective thrombin binding and thrombophilia. Homozygous substitution of B beta 68 Ala—Thr. J Clin Invest 1992; 90 (01) 238-244
    Search in Google Scholar
  • 17 Lord ST, Strickland E, Jayjock E. Strategy for recombinant multichain protein synthesis: fibrinogen B beta-chain variants as thrombin substrates. Biochemistry 1996; 35 (07) 2342-2348
    CrossrefPubMedSearch in Google Scholar
  • 18 Mullin JL, Gorkun OV, Lord ST. Decreased lateral aggregation of a variant recombinant fibrinogen provides insight into the polymerization mechanism. Biochemistry 2000; 39 (32) 9843-9849
    CrossrefPubMedSearch in Google Scholar
  • 19 Yoshida S, Kibe T, Matsubara R. et al. Congenital dysfibrinogenemia in a Japanese family with fibrinogen Naples (BβAla68Thr) manifesting as superior sagittal sinus thrombosis. Blood Coagul Fibrinolysis 2017; 28 (07) 580-584
    CrossrefPubMedSearch in Google Scholar
  • 20 Pechik I, Madrazo J, Mosesson MW, Hernandez I, Gilliland GL, Medved L. Crystal structure of the complex between thrombin and the central “E” region of fibrin. Proc Natl Acad Sci U S A 2004; 101 (09) 2718-2723
    CrossrefPubMedSearch in Google Scholar