The dysfunction of coagulation factor VIIPadua results from substitution of arginine-304 by glutamine.

This study addresses whether a mutation in the factor VIIPadua gene could explain the reduced activity of the inherited variant protein. All nine exons of the normal and Padua factor VII gene were amplified using the polymerase chain reaction, cloned into pUC19 and sequenced. A point mutation (G to A at nucleotide position 10828) was found which results in the substitution of a glutamine (CAG) for arginine (CGG) at amino acid position 304. This substitution creates a PvuII restriction site useful in screening for the defect and in demonstrating homozygosity. This substitution involves an arginine residue in the catalytic domain within a LeuPro*Cys motif which occurs in conserved region 5 in up to 16 coagulation and other serine proteinases. On the basis of conformational homology among serine proteinases, it is suggested that the observed amino acid substitution in factor VIIPadua could cause structural changes affecting its activation and/or catalytic activity.