In a 47-year-old man with no clinical bleeding tendency but with undetectable plasma factor VII activity when tested in a 1-stage assay using rabbit brain tissue factor, O'Brien et al. (1991) identified a heterozygous G-to-A transition in the F7 gene, resulting in an arg304-to-gln (R304Q) substitution. Plasma from the patient showed normal factor VII antigen levels. Residue arg304 is homologous to arg333 of factor IX, and an arg333-to-gln mutation in F9 (300746.0056) has been identified in patients with severe hemophilia B (306900) in whom there is synthesis and expression of the factor IX protein.
Marchetti et al. (1992) identified a heterozygous R304Q substitution in the F7 gene as the basis of abnormal factor VII Padua, described by Girolami et al. (1982) in persons originating from the Piave River valley in northeastern Italy. The individuals described by Girolami et al. (1982) were asymptomatic, but presented a mild prolongation of prothrombin time. Factor VII activity varied between 45% and 61% of normal, but factor VII cross-reacting material was normal. A good negative correlation was found between factor VII level and prothrombin times.
