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

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.

Automated summary

This study identified two new mutations of the fibrinogen beta-chain in patients with inherited fibrinogen deficiency, showing that these mutations lead to low fibrinogen levels in patients and genetic modifiers that affect their global hemostatic function. These results provide clinically relevant information for personalized patient management and precision medicine for fibrinogen disorders.