A heterozygous nonsense mutation in the FGB gene (c.1299G > A) causes congenital fibrinogen disorder across four consecutive generations.

The aim of this study was to elucidate the molecular abnormalities in a four-generation Chinese family affected by congenital fibrinogen disorder (CFD). The proband was a 5-year-old Chinese boy with CFD. Routine clotting tests revealed decreased plasma fibrinogen concentration in the proband and in his father and sister. Notably, the condition presented was clinically asymptomatic. Whole exome sequencing identified a heterozygous c.1299G > A mutation in exon 8 of the FGB gene, leading to p.Trp433* (TGG > TGA). Further Sanger sequencing revealed the presence of this mutation in his great-grandmother, grandfather, father, and sister as well. The FGB gene variant c.1299G > A (p.Trp433*) across four consecutive generations is associated with CFD.