Introduction: Congenital afibrinogenemia , a rare autosomal recessive disorder associated with a complete absence of fibrinogen in the bloodstream.Uncontrollable bleeding from the umbilical cord after birth is the most common symptom. Fibrinogen or coagulation factor 1 is a plasma-soluble glycoprotein, which is converted into fibrin strands in the coagulation cascade by thrombin.
This protein consists of three chains Aα, β B and γ, each polypeptide is coded by a separate gene. Fibrinogen genes are clustered together on chromosome 4q28-31.In this study, the aim is to investigate the three missense mutations L383R in exon 7, G430D in exon 8, and R258H in exon 6 in the C-terminal part of fibrinogen β chain
Methods: In this article, Gene Runner, PAYMOL software and NCBI, SWISS-MODEL, PDB and UniProt databases are used to show the changes caused by this mutation on fibrinogen β protein.
Results: There are three nonsense mutations L383R in exon 7, G430D in exon 8, and R258H in exon 6 in the C-terminal part of fibrinogen β chain, which lead to decreased secretion of hexameric fibrinogen β complex
Conclusion: These mutations lead to a decrease in the secretion of hexameric fibrinogen β complex due to improper packing of β chains and improper folding of these chains.