A case of congenital afibrinogenemia: Fibrinogen Hakata, a novel nonsense mutation of the fibrinogen gamma-chain gene

Congenital afibrinogenemia due to a novel homozygous nonsense mutation of t he fibrinogen gamma-chain gene, fibrinogen Hakata, was found in an 18-year- old Japanese girl who had received supplemental fibrinogen therapy since sh e was 4 months old. The plasma fibrinogen concentrations of the proband wer e measured as less than 10 mg/dl by a functional method and less than 17 mg /dl by an immunological method. Fibrinogen concentrations of her family wer e in the range of 94-164 mg/dl. The proband and her family had no other cli nical symptoms. Genomic DNA of the proband and her family was isolated from leukocytes, and all exons of fibrinogen subunits and their intron/exon boundaries were ana lyzed. A genetic mutation, a guanine-to-thymine (G-to-T) transversion at th e nucleotide position of 5860, was identified on exon 7 of the gamma-chain gene. This mutation changed the codon for the 231st residue of the gamma ch ain from GAG (Glu) to TAG (stop). No other mutation was observed. A alpha, B beta and gamma chains were observed in plasma of the heterozygous family members. However, only a trace amount of A alpha chain and no gamma chain w as detected in the plasma of the proband.