Factor VII deficiency due to compound heterozygosity for Leu-48Pro mutation and a novel Pro260Leu mutation

We investigated the mechanisms responsible for factor VII (FVII) deficiency in a compound heterozygous Japanese patient with mutations both in the signal peptide and in the catalytic domain. FVII activity (FVII:C) and antigen (FVII:Ag) levels of the patient were 14.5% and 12.5% of those of the normal controls, respectively. In all, 2 heterozygous point mutations were identified in the patient: one was the mutation substituting Pro for Leu-48 in the prepeptide domain of FVII; the other one was a novel mutation substituting Leu for Pro260 in the catalytic domain. FVII activity and FVII:Ag levels in the condition medium that transiently coexpressed the 2 different FVII mutants in baby hamster kidney (BHK) cells were 4.81% and 5.18% of the wild-type FVII. Factor VII defect of the patient may be combined with both impairing endoplasmic reticulum (ER) targeting and altering FVII folding/biosynthesis, but cotransfection of 2 different FVII mutants may interfere with their expression in BHK cells.