Mutations in the fibrinogen Aα-chain gene identified in the analyzed patients with congenital afibrinogenemia.

(A) Schematic representation of the fibrinogen Aα-chain gene showing the positions of the identified mutations. Heterozygous mutations are shown in italics; homozygous mutations are shown in bold. Exons (numbered) and introns are indicated by boxes and narrow lines, respectively, and are drawn to scale. The shaded portions of exons represent the regions where a premature termination codon should not induce nonsense-mediated mRNA decay. Exon 6 of Aα-chain gene, which is present only in 2% of transcripts, has been omitted. (B) Predicted effects of the identified mutations at the protein level. Schematic representations of the fibrinogen Aα-chain (omitting the signal peptide encoded by exon 1) and of the predicted mutant truncated polypeptides are shown. Portions of Aα-chain encoded by different exons are drawn to scale and shaded in different grays. Numbers above the schematic drawing of the mature Aα-chain refer to amino acid positions corresponding to exon/exon boundaries; numbers beside the truncated polypeptides refer to their amino acid lengths.