Hypofibrinogenemia caused by a nonsense mutation in the fibrinogen Bbeta chain gene.

Summary.  Congenital hypofibrinogenemia, fibrinogen Tottori II, caused by a nonsense mutation in the fibrinogen Bβ chain gene, was found in a 68-year-old Japanese female. The plasma fibrinogen level was 99.2 mg dL−1 as determined by the thrombin time method. No overt molecular abnormalities were observed in purified patient fibrinogen by SDS–PAGE analysis. After sequencing all exons and exon–intron boundaries of three fibrinogen genes, we found a heterozygous single point mutation of TG at position 3356 of the patient fibrinogen Bβ chain gene. This nucleotide mutation results in a nonsense mutation (TAT sequence for Bβ 41Tyr to TAG sequence for a translation termination signal). The mutation was confirmed by polymerase chain reaction-restriction fragment length polymorphism analysis, since this nucleotide mutation results in a new NheI recognition sequence at this position. These data indicated that the nonsense mutation of the fibrinogen Bβ chain gene caused a truncated fibrinogen Bβ chain, which may not be assembled in the fibrinogen molecule.