Homozygous F5 deep-intronic splicing mutation resulting in severe factor V deficiency and undetectable XXXX generation in platelet-rich plasma.

@entity2244 @entity1 @entity932 @entity121 @entity556 @entity548 @entity73113 @entity5631 @entity942
BACKGROUND: Coagulation factor (F) @entity2244 is associated with a @entity548 tendency of variable severity, but phenotype determinants are largely unknown. Recently, we have shown that three @entity1 with undetectable plasma FV and mild @entity548 symptoms had sufficient residual platelet FV to support @entity556 generation in platelet-rich plasma (PRP). Therefore, we hypothesized that @entity942 @entity1 with severe @entity548 manifestations may lack platelet FV. OBJECTIVES: To characterize a @entity942 @entity1 with a severe @entity548 diathesis. @entity1 /METHODS: We performed FV mutation screening and functional studies in a 31-year-old male (FV:C < 1%) with umbilical @entity548 at birth, recurrent @entity5631 and @entity121 , and a recent @entity932 . RESULTS: The proband was homozygous for a deep-intronic mutation (F5 @entity73113 ) causing the inclusion of a pseudo-exon with an in-frame stop codon in the mature F5 mRNA. Although platelet FV antigen was detectable by immunoprecipitation followed by Western blotting, no FV activity could be demonstrated in the proband's plasma or platelets with a prothrombinase-based assay. Moreover, no @entity556 generation was observed in PRP triggered with 1-50 pm tissue factor (even in the presence of platelet agonists), whereas an acquired FV inhibitor was excluded. Clot formation in the proband's whole blood, as assessed by thromboelastometry, was markedly delayed but not abolished. CONCLUSIONS: This is the first report of a pathogenic deep-intronic mutation in the F5 gene. Our findings indicate that the minimal FV requirement for viability is extremely low and suggest that @entity556 generation in PRP may predict @entity548 tendency in @entity1 with undetectable plasma FV.
