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Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis
Congenital fibrinogen disorders are diseases associated with a bleeding tendency; however, there are also reports of thrombotic events. Fibrinogen plays a role in the pathogenesis of thrombosis due to altered plasma concentrations or modifications to fibrinogen’s structural properties, which affect...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874973/ https://www.ncbi.nlm.nih.gov/pubmed/35207353 http://dx.doi.org/10.3390/jcm11041083 |
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author | Brunclikova, Monika Simurda, Tomas Zolkova, Jana Sterankova, Miroslava Skornova, Ingrid Dobrotova, Miroslava Kolkova, Zuzana Loderer, Dusan Grendar, Marian Hudecek, Jan Stasko, Jan Kubisz, Peter |
author_facet | Brunclikova, Monika Simurda, Tomas Zolkova, Jana Sterankova, Miroslava Skornova, Ingrid Dobrotova, Miroslava Kolkova, Zuzana Loderer, Dusan Grendar, Marian Hudecek, Jan Stasko, Jan Kubisz, Peter |
author_sort | Brunclikova, Monika |
collection | PubMed |
description | Congenital fibrinogen disorders are diseases associated with a bleeding tendency; however, there are also reports of thrombotic events. Fibrinogen plays a role in the pathogenesis of thrombosis due to altered plasma concentrations or modifications to fibrinogen’s structural properties, which affect clot permeability, resistance to lysis, and its stiffness. Several distinct types of genetic change and pathogenetic mechanism have been described in patients with bleeding and a thrombotic phenotype, including mutations affecting synthesis or processing in three fibrinogen genes. In this paper, we focused on familial hypofibrinogenemia, a rare inherited quantitative fibrinogen disorder characterized by decreased fibrinogen levels with a high phenotypic heterogeneity. To begin, we briefly review the basic information regarding fibrinogen’s structure, its function, and the clinical consequences of low fibrinogen levels. Thereafter, we introduce 15 case reports with various gene mutations derived from the fibrinogen mutation database GFHT (French Study Group on Hemostasis and Thrombosis), which are associated with congenital hypofibrinogenemia with both bleeding and thrombosis. Predicting clinical presentations based on genotype data is difficult. Genotype–phenotype correlations would be of help to better understand the pathologic properties of this rare disease and to provide a valuable tool for the identification of patients who are not only at risk of bleeding, but also at risk of a thrombotic event. |
format | Online Article Text |
id | pubmed-8874973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88749732022-02-26 Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis Brunclikova, Monika Simurda, Tomas Zolkova, Jana Sterankova, Miroslava Skornova, Ingrid Dobrotova, Miroslava Kolkova, Zuzana Loderer, Dusan Grendar, Marian Hudecek, Jan Stasko, Jan Kubisz, Peter J Clin Med Review Congenital fibrinogen disorders are diseases associated with a bleeding tendency; however, there are also reports of thrombotic events. Fibrinogen plays a role in the pathogenesis of thrombosis due to altered plasma concentrations or modifications to fibrinogen’s structural properties, which affect clot permeability, resistance to lysis, and its stiffness. Several distinct types of genetic change and pathogenetic mechanism have been described in patients with bleeding and a thrombotic phenotype, including mutations affecting synthesis or processing in three fibrinogen genes. In this paper, we focused on familial hypofibrinogenemia, a rare inherited quantitative fibrinogen disorder characterized by decreased fibrinogen levels with a high phenotypic heterogeneity. To begin, we briefly review the basic information regarding fibrinogen’s structure, its function, and the clinical consequences of low fibrinogen levels. Thereafter, we introduce 15 case reports with various gene mutations derived from the fibrinogen mutation database GFHT (French Study Group on Hemostasis and Thrombosis), which are associated with congenital hypofibrinogenemia with both bleeding and thrombosis. Predicting clinical presentations based on genotype data is difficult. Genotype–phenotype correlations would be of help to better understand the pathologic properties of this rare disease and to provide a valuable tool for the identification of patients who are not only at risk of bleeding, but also at risk of a thrombotic event. MDPI 2022-02-18 /pmc/articles/PMC8874973/ /pubmed/35207353 http://dx.doi.org/10.3390/jcm11041083 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Brunclikova, Monika Simurda, Tomas Zolkova, Jana Sterankova, Miroslava Skornova, Ingrid Dobrotova, Miroslava Kolkova, Zuzana Loderer, Dusan Grendar, Marian Hudecek, Jan Stasko, Jan Kubisz, Peter Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis |
title | Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis |
title_full | Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis |
title_fullStr | Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis |
title_full_unstemmed | Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis |
title_short | Heterogeneity of Genotype–Phenotype in Congenital Hypofibrinogenemia—A Review of Case Reports Associated with Bleeding and Thrombosis |
title_sort | heterogeneity of genotype–phenotype in congenital hypofibrinogenemia—a review of case reports associated with bleeding and thrombosis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874973/ https://www.ncbi.nlm.nih.gov/pubmed/35207353 http://dx.doi.org/10.3390/jcm11041083 |
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