Factor X M402T: a homozygous missense mutation identified as the cause of cross-reacting material-reduced deficiency.

ABSTRACT

We investigated a mildly hemorrhagic patient with factor X (FX) deficiency to identify the nature of his defect by comprehensive analyses. A 42-year-old Japanese man was admitted to our hospital for uncontrolled gingival hemorrhage. His FX activity based on prothrombin time (PT) and activated partial thromboplastin time (aPTT) and FX antigen were <1, 6.5 and 11 %, respectively. A homozygous M402T missense mutation (c.1205 t>c; p.Met402Thr) was identified in the FX gene (F10) from both the patient and his brother. The mutation was not detected in the F10 of 82 unrelated normal Japanese individuals. We studied the functional consequences of this mutation by expressing mutant FX-M402T protein in HEK293 cells. This analysis revealed that the antigen of the FX-M402T mutants was approximately 26 % that of the wild-type FX in conditioned media. The FX-specific activity of FX-M402T mutants measured by a one-stage clotting assay based upon PT and aPTT, and a chromogenic assay using Russell's viper venom in the concentrated media was 7.7, 31.7, and 41.2 % of wild type, respectively. The results suggest that the mutation FX-M402T may cause a secretion defect and a molecular abnormality in FX.