A Case of Congenital Afibrinogenemia: Fibrinogen Hakata, a Novel Nonsense Mutation of the Fibrinogen γ-Chain Gene

Summary

Congenital afibrinogenemia due to a novel homozygous nonsense mutation of the fibrinogen γ-chain gene, fibrinogen Hakata, was found in an 18-year-old Japanese girl who had received supplemental fibrinogen therapy since she was 4 months old. The plasma fibrinogen concentrations of the proband were 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 were in the range of 94-164 mg/dl. The proband and her family had no other clinical 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 analyzed. A genetic mutation, a guanine-to-thymine (G-to-T) transversion at the nucleotide position of 5860, was identified on exon 7 of the γ-chain gene. This mutation changed the codon for the 231st residue of the γ chain from GAG (Glu) to TAG (stop). No other mutation was observed. Aα, Bβ and γ chains were observed in plasma of the heterozygous family members. However, only a trace amount of Aα chain and no γ chain was detected in the plasma of the proband.

Keywords

Afibrinogenemia - γ chain of fibrinogen - nonsense mutation - gene analysis

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