Factor VII C329R: a variant with a disrupted disulfide bond in the catalytic domain

We report a novel mutation within the coagulation factor VII gene associated with a dysfunctional procoagulant factor VII (12% of normal plasma factor VII activity; 50% of normal plasma factor VII antigen level). Using heteroduplex analysis and subsequent sequencing, we identified a thymine-10,902 to cytosine mutation within exon eight of the factor VII gene, encoding for a substitution of arginine for cysteine-329 (factor VII C329R) within the heavy chain of factor VII. This substitution disrupts a disulfide bond within the factor VII catalytic domain and might cause altered conformation of the active site triad.