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 a n essential role in blood coagulation. Individuals deficient in this protei n 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 exo n V is absent. Some individuals deficient in plasma FXI produce the platele t 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 plat elet FXI. All three individuals had a nonsense mutation encoding a stop cod on in exon V of the FXI gene that would result in a severely truncated poly peptide. An exon V nonsense mutation in the FXI gene combined with the abse nce of exon V in platelet FXI mRNA provides a plausible mechanism for the d ifferential expression of platelet FXI in plasma FXI-deficient patients.