Analysis of phenotype and genotype of a family with hereditary coagulation factor V deficiency caused by the compound heterozygous mutations

To analyze the causative gene and the molecular pathogenesis in a pedigree with compound hereditary coagulation factor V deficiency. Routine blood coagulation indexes and factor V antigen (FV:Ag) were detected by the one-stage clotting method and ELISA. Function of the mutant protein was evaluated by the method Calibrated Automated Thrombogram (CAT). The factor V gene was amplified by PCR with direct sequencing. The possible impact of the mutations were analyzed by bioinformatics tools. The proband's factor V activity and FV:Ag were reduced to 3 and 6%. Gene sequencing revealed compound heterozygous mutations c.911G>A (Gly276Glu) in exon 6 and c.5343C>G (Ser1781Arg) in exon 16. The thrombin generation test showed that the mutant protein markedly decreased thrombin. Bioinformatics indicated that mutations were deleterious. The compound heterozygous mutations Gly276Glu and Ser1781Arg were responsible for the decrease of factor V activity and FV:Ag, of which Ser1781Arg was first reported in the world.