Analysis of the novel factor X gene mutation Glu51Lys in two families with factor X-Riyadh anomaly

Two families with 'factor X(FX)-Riyadh' have been identified (one of them related to the originally reported family). Affected members of both families exhibit prolongation in prothrombin time (PT) with normal partial thromboplastin time (PTT) and low assay levels of FX, when measured by PT-based assay. They do not have clinical bleeding diathesis, regardless of the PT prolongation. FX genes of the affected family members were analyzed by sequence analysis. A novel missense mutation in exon 4 of the FX gene, which causes the Glu5ILys substitution in the first epidermal growth factor-like domain of FX was found. The Glu5ILys mutation represents a type 11 mutation with low FX coagulant activity in the extrinsic pathway and normal FX antigen levels. This mutation may result in disruption of the predicted H-bonding between residue Glu5I of FX and the Asn 199 residue of the tissue factor (TF) in the FX/TF/factorVIIa ternary complex, producing the phenotype TX deficiency Riyadh', with prolonged PT and normal PTT.