A novel fibrinogen B beta chain frameshift mutation causes congenital afibrinogenaemia

Area of Science:

• Genetics
• Hematology
• Molecular Biology

Background:

• Congenital afibrinogenemia is a rare autosomal recessive bleeding disorder.
• It results from mutations in fibrinogen genes (FGA, FGB, FGG).
• Insertions/deletions in the FGB gene are exceptionally rare.

Observation:

• A patient presented with severe umbilical cord bleeding and recurrent bleeding episodes.
• Plasma fibrinogen levels were undetectable by Clauss and immunological assays.
• Molecular analysis identified homozygosity for a novel four-base insertion (g. 2833_2834 ins GTTT) in FGB exon 2.

Findings:

• The FGB mutation resulted in a truncated polypeptide with abnormal residues.
• Transient expression showed mutant fibrinogen accumulated in cell lysates but not secreted into media.
• This suggests the mutation impairs fibrinogen assembly and secretion.

Implications:

• This novel FGB mutation is likely responsible for congenital afibrinogenemia in the reported patient.
• The findings highlight the critical role of FGB in fibrinogen secretion.
• Understanding genotype-phenotype correlations aids in diagnosing and managing rare bleeding disorders.