Nonsense mutation in exon V of the factor XI gene does not abolish platelet factor XI expression.

Factor XI (FXI) is a plasma glycoprotein produced by the liver that plays an essential role in blood coagulation. Individuals deficient in this protein are prone to bleeding following trauma or surgery. Well-washed platelets possess FXI-like activity and FXI antigen that differs in molecular weight from plasma FXI and is associated with FXI mRNA from platelets in which exon V is absent. Some individuals deficient in plasma FXI produce the platelet form of the protein. The molecular basis for the presence of platelet FXI in plasma FXI-deficient patients is unknown. In the current study, to help determine the mechanism for this differential expression, the FXI genotype was determined for three plasma FXI-deficient individuals who express platelet FXI. All three individuals had a nonsense mutation encoding a stop codon in exon V of the FXI gene that would result in a severely truncated polypeptide. An exon V nonsense mutation in the FXI gene combined with the absence of exon V in platelet FXI mRNA provides a plausible mechanism for the differential expression of platelet FXI in plasma FXI-deficient patients.