title: Nonsense mutation in exon V of the factor XI gene does not abolish platelet factor XI expression.
abstract: 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.
authors.affiliation: Sol Sherry Thrombosis Research Center, University of Pennsylvania, Temple University School of Medicine, Philadelphia 19140, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Shirk
authors.forename: B A
authors.initials: BA
authors.lastname: Konkle
authors.forename: P N
authors.initials: PN
authors.lastname: Walsh
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D005091:Exons; D005172:Factor XI / Q000235:genetics* / Q000378:metabolism; D005173:Factor XI Deficiency / Q000097:blood / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA
chemical_list: D005172:Factor XI