Background
Congenital hypofibrinogenemia, a quantitative fibrinogen disorder, is characterized by abnormally low levels of both functional and antigen fibrinogen. We identified a heterozygous nonsense mutation, p.Arg17Stop, in the fibrinogen Bβ chain of a three-month-old female infant.
Conclusions
The p.Arg17Stop mutation in the fibrinogen Bβ chain disrupts fibrinogen production and secretion, contributing to hypofibrinogenemia.
Methods
Coagulation testing, gene analysis, in vitro plasmid construction, and functional analyses were conducted to investigate the underlying pathogenic mechanisms.
Results
Plasma fibrinogen levels showed decrease in the proband. DNA sequencing of the proband revealed a heterozygous point mutation (c.139C>T) in exon 2 of the FGB gene causing Arg → Stop substitution. Human Arg17 was found to be highly conserved. In vitro expression analyses indicated that the mutation impacts both the transcription and translation of the FGB gene, subsequently affecting the synthesis and secretion of fibrinogen. Conclusions: The p.Arg17Stop mutation in the fibrinogen Bβ chain disrupts fibrinogen production and secretion, contributing to hypofibrinogenemia.