SYMPTOMATIC HEREDITARY TYPE-II PROTEIN-C DEFICIENCY CAUSED BY A MISSENSE MUTATION IN EXON-IX OF THE PROTEIN-C GENE (GLY381 TO SER)

We report the characterization of the genetic defect in a family with hereditary type-II protein C (PC) deficiency. The propositus is a 28-y ear-old woman with a history of thrombosis. Her PC activity level (58% ) and PC antigen level (115%) are comptible with the diagnosis of type -II PC deficiency. Her asymptomatic sister is also PC deficient. Analy sis of the PC gene of the propositus revealed a point mutation (G to A ) at nucleotide 8856, which results in the replacement of Gly381 by Se r in the heavy chain of PC. The amino acid change occurs close to the active-site serine at a residue which is highly conserved among the se rine proteases. The mutation is also present in the PC gene of the pro positus' sister. Her brother, who is asymptomatic, has a normal genoty pe with respect to the mutation at nucleotide 8856.