Rescue of activated protein C-resistance phenotype by cis-acting factor V Gly2032Asp mutation

Abstract

A 60-year-old Italian woman presenting with factor VLeiden mutation but a normal activated protein C (APC) resistance, low functional and antigenic factor (FV) plasma levels, was found to have a novel heterozygous Gly2032Asp substitution located on the same allele. In transfected cells, the Gly2032Asp mutation caused an approximately 2-fold reduction of the intracellular FV protein and a 9-fold reduction of the secreted protein, suggesting that the Gly2032Asp substitution acts in cis on the allele carrying the FVLeiden mutation and rescues the APC-resistance phenotype.