A novel nonsense mutation in the FGA gene in a Chinese family with congenital afibrinogenaemia.

Congenital afibrinogenaemia is a rare autosomal recessive coagulation disorder. Here we describe the genetic defect in the fibrinogen A alpha-chain underlying afibrinogenaemia in a Chinese family. The proposita had a life-long bleeding tendency, both her parents and paternal grandparents had a consanguineous marriage. The blood-clotting indices of the proposita and her father were prolonged, and their functional and immunologic fibrinogen was absent. To identify the mutations of fibrinogen genes in this family, all the exons and exon-intron boundaries of the three fibrinogen genes (FGA, FGB, FGG) were amplified by polymerase chain reaction, and direct sequencing of polymerase chain reaction products was performed, then the restriction endonuclease (RsaI) analysis was used to confirm the mutation. A homozygous C --> T mutation was found at nucleotide 3108 in exon 4 of the FGA gene of the proposita and her father; it is a null mutation predicting to produce severely truncated A alpha-chains because of the presence of premature termination at the Gln 150 codon (or truncated at the 131 residues according to the mature A alpha-chain). Her mother and some other family members were heterozygous. The g.3108C --> T (Gln150 --> stop) nonsense mutation in the FGA gene is a novel genetic defect of congenital afibrinogenaemia that, to our knowledge, has not been described previously.