Novel missense mutations affecting the structure of the conserved fibrinogen Bβ C-terminal domain cause congenital hypofibrinogenemia.

Abstract

This study describes the identification of two new mutations of the fibrinogen beta-chain in patients with inherited fibrinogen deficiency. Modelling of the impact of the mutations predict that these single amino acid substitutions are sufficient to abolish secretion of the mutant chains into the circulation, resulting in low fibrinogen levels in the patients. In addition, whole exome sequencing identified genetic modifiers for both patients which could contribute to the patients' global hemostatic function. Our results yield clinically relevant information for the personalised management of patients and eventually precision medicine for fibrinogen disorders.

• Authors: Raquel Bártolo, Maxime Arbez, Rui Vilar, Timea Szanto, Elina Lehtinen, Nathalie Trillot, Antoine Rauch, Alessandro Casini, Marguerite Neerman-Arbez
• Journal: Thrombosis research (Thromb Res) Vol. 206 Pg. 5-8 (10 2021) ISSN: 1879-2472 [Electronic] United States
• PMID: 34352655 (Publication Type: Letter)
• Copyright: Copyright © 2021 Elsevier Ltd. All rights reserved.

Chemical References

• BBeta fibrinogen
• Fibrinogen

Topics

• Afibrinogenemia (genetics)
• Amino Acid Substitution
• Fibrinogen (genetics)
• Humans
• Mutation, Missense