Genetic Variants in the <i>FGB</i> and <i>FGG</i> Genes Mapping in the Beta and Gamma Nodules of the Fibrinogen Molecule in Congenital Quantitative Fibrinogen Disorders Associated with a Thrombotic Phenotype
Fibrinogen is a hexameric plasmatic glycoprotein composed of pairs of three chains (Aα, Bβ, and γ), which play an essential role in hemostasis. Conversion of fibrinogen to insoluble polymer fibrin gives structural stability, strength, and adhesive surfaces for growing blood clots. Equally important,...
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MDPI AG
2020-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/13/4616 |
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| author | Tomas Simurda Monika Brunclikova Rosanna Asselta Sonia Caccia Jana Zolkova Zuzana Kolkova Dusan Loderer Ingrid Skornova Jan Hudecek Zora Lasabova Jan Stasko Peter Kubisz |
| author_facet | Tomas Simurda Monika Brunclikova Rosanna Asselta Sonia Caccia Jana Zolkova Zuzana Kolkova Dusan Loderer Ingrid Skornova Jan Hudecek Zora Lasabova Jan Stasko Peter Kubisz |
| author_sort | Tomas Simurda |
| collection | DOAJ |
| description | Fibrinogen is a hexameric plasmatic glycoprotein composed of pairs of three chains (Aα, Bβ, and γ), which play an essential role in hemostasis. Conversion of fibrinogen to insoluble polymer fibrin gives structural stability, strength, and adhesive surfaces for growing blood clots. Equally important, the exposure of its non-substrate thrombin-binding sites after fibrin clot formation promotes antithrombotic properties. Fibrinogen and fibrin have a major role in multiple biological processes in addition to hemostasis and thrombosis, i.e., fibrinolysis (during which the fibrin clot is broken down), matrix physiology (by interacting with factor XIII, plasminogen, vitronectin, and fibronectin), wound healing, inflammation, infection, cell interaction, angiogenesis, tumour growth, and metastasis. Congenital fibrinogen deficiencies are rare bleeding disorders, characterized by extensive genetic heterogeneity in all the three genes: <i>FGA</i>, <i>FGB</i>, and <i>FGG</i> (enconding the Aα, Bβ, and γ chain, respectively). Depending on the type and site of mutations, congenital defects of fibrinogen can result in variable clinical manifestations, which range from asymptomatic conditions to the life-threatening bleeds or even thromboembolic events. In this manuscript, we will briefly review the main pathogenic mechanisms and risk factors leading to thrombosis, and we will specifically focus on molecular mechanisms associated with mutations in the C-terminal end of the beta and gamma chains, which are often responsible for cases of congenital afibrinogenemia and hypofibrinogenemia associated with thrombotic manifestations. |
| first_indexed | 2024-03-10T18:49:12Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T18:49:12Z |
| publishDate | 2020-06-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-387723c270a74da99a2b53ab44313bbf2023-11-20T05:17:45ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012113461610.3390/ijms21134616Genetic Variants in the <i>FGB</i> and <i>FGG</i> Genes Mapping in the Beta and Gamma Nodules of the Fibrinogen Molecule in Congenital Quantitative Fibrinogen Disorders Associated with a Thrombotic PhenotypeTomas Simurda0Monika Brunclikova1Rosanna Asselta2Sonia Caccia3Jana Zolkova4Zuzana Kolkova5Dusan Loderer6Ingrid Skornova7Jan Hudecek8Zora Lasabova9Jan Stasko10Peter Kubisz11National Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, SlovakiaNational Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, SlovakiaDepartment of Biomedical Sciences, Humanitas University, 20090 Pieve Emanuele, ItalyDepartment of Biomedical and Clinical Sciences”L. Sacco”, Università degli Studi di Milano, 20157 Milan, ItalyNational Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, SlovakiaBiomedical Center Martin, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, 03601 Martin, SlovakiaBiomedical Center Martin, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, 03601 Martin, SlovakiaNational Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, SlovakiaNational Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, SlovakiaDepartment of Molecular Biology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin, 03601 Martin, SlovakiaNational Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, SlovakiaNational Center of Hemostasis and Thrombosis, Department of Hematology and Transfusiology, Comenius University in Bratislava, Jessenius Faculty of Medicine in Martin and University Hospital in Martin, 03601 Martin, SlovakiaFibrinogen is a hexameric plasmatic glycoprotein composed of pairs of three chains (Aα, Bβ, and γ), which play an essential role in hemostasis. Conversion of fibrinogen to insoluble polymer fibrin gives structural stability, strength, and adhesive surfaces for growing blood clots. Equally important, the exposure of its non-substrate thrombin-binding sites after fibrin clot formation promotes antithrombotic properties. Fibrinogen and fibrin have a major role in multiple biological processes in addition to hemostasis and thrombosis, i.e., fibrinolysis (during which the fibrin clot is broken down), matrix physiology (by interacting with factor XIII, plasminogen, vitronectin, and fibronectin), wound healing, inflammation, infection, cell interaction, angiogenesis, tumour growth, and metastasis. Congenital fibrinogen deficiencies are rare bleeding disorders, characterized by extensive genetic heterogeneity in all the three genes: <i>FGA</i>, <i>FGB</i>, and <i>FGG</i> (enconding the Aα, Bβ, and γ chain, respectively). Depending on the type and site of mutations, congenital defects of fibrinogen can result in variable clinical manifestations, which range from asymptomatic conditions to the life-threatening bleeds or even thromboembolic events. In this manuscript, we will briefly review the main pathogenic mechanisms and risk factors leading to thrombosis, and we will specifically focus on molecular mechanisms associated with mutations in the C-terminal end of the beta and gamma chains, which are often responsible for cases of congenital afibrinogenemia and hypofibrinogenemia associated with thrombotic manifestations.https://www.mdpi.com/1422-0067/21/13/4616fibrinogenquantitative fibrinogen disordersbeta and gamma nodules<i>FGB</i> gene<i>FGG</i> genemutations associated with thrombosis |
| spellingShingle | Tomas Simurda Monika Brunclikova Rosanna Asselta Sonia Caccia Jana Zolkova Zuzana Kolkova Dusan Loderer Ingrid Skornova Jan Hudecek Zora Lasabova Jan Stasko Peter Kubisz Genetic Variants in the <i>FGB</i> and <i>FGG</i> Genes Mapping in the Beta and Gamma Nodules of the Fibrinogen Molecule in Congenital Quantitative Fibrinogen Disorders Associated with a Thrombotic Phenotype International Journal of Molecular Sciences fibrinogen quantitative fibrinogen disorders beta and gamma nodules <i>FGB</i> gene <i>FGG</i> gene mutations associated with thrombosis |
| title | Genetic Variants in the <i>FGB</i> and <i>FGG</i> Genes Mapping in the Beta and Gamma Nodules of the Fibrinogen Molecule in Congenital Quantitative Fibrinogen Disorders Associated with a Thrombotic Phenotype |
| title_full | Genetic Variants in the <i>FGB</i> and <i>FGG</i> Genes Mapping in the Beta and Gamma Nodules of the Fibrinogen Molecule in Congenital Quantitative Fibrinogen Disorders Associated with a Thrombotic Phenotype |
| title_fullStr | Genetic Variants in the <i>FGB</i> and <i>FGG</i> Genes Mapping in the Beta and Gamma Nodules of the Fibrinogen Molecule in Congenital Quantitative Fibrinogen Disorders Associated with a Thrombotic Phenotype |
| title_full_unstemmed | Genetic Variants in the <i>FGB</i> and <i>FGG</i> Genes Mapping in the Beta and Gamma Nodules of the Fibrinogen Molecule in Congenital Quantitative Fibrinogen Disorders Associated with a Thrombotic Phenotype |
| title_short | Genetic Variants in the <i>FGB</i> and <i>FGG</i> Genes Mapping in the Beta and Gamma Nodules of the Fibrinogen Molecule in Congenital Quantitative Fibrinogen Disorders Associated with a Thrombotic Phenotype |
| title_sort | genetic variants in the i fgb i and i fgg i genes mapping in the beta and gamma nodules of the fibrinogen molecule in congenital quantitative fibrinogen disorders associated with a thrombotic phenotype |
| topic | fibrinogen quantitative fibrinogen disorders beta and gamma nodules <i>FGB</i> gene <i>FGG</i> gene mutations associated with thrombosis |
| url | https://www.mdpi.com/1422-0067/21/13/4616 |
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