title: Type II protein C deficiency: identification and molecular modelling of two natural mutants with low anticoagulant and normal amidolytic activity.
abstract: Two mutations in exons 3 and 9 of the protein C gene were identified by amplification and sequencing from symptomatic probands referred for venous thromboembolism and thrombophilia screening. The phenotype associated with the mutations is a type II protein C deficiency with normal amidolytic activity. In one family, the mutation in exon 3 (G3545-->A), which predicts an R9 to H substitution in the Gla domain, was identified. A mutation in exon 9 (G10899-->A), which predicts an R352 to W substitution in the catalytic site, was identified in the second family and has been reported previously in association with type II deficiency with low amidolytic activity. Western blotting of the purified proteins from the probands' plasma did not show any abnormal migratory pattern. Molecular modelling suggested a possible impairment in the recently described Na+ binding pocket for the R352-->W mutant. No conclusions could be drawn relative to the R9-->H mutant.
authors.affiliation: Angelo Bianchi Bonomi Haemophilia and Thrombosis Centre, IRCCS Maggiore Hospital and Institute of Internal Medicine, University of Milan, Italy.
authors.forename: E M
authors.initials: EM
authors.lastname: Faioni
authors.forename: J
authors.initials: J
authors.lastname: Hermida
authors.forename: E
authors.initials: E
authors.lastname: Rovida
authors.forename: C
authors.initials: C
authors.lastname: Razzari
authors.forename: D
authors.initials: D
authors.lastname: Asti
authors.forename: S
authors.initials: S
authors.lastname: Zeinali
authors.forename: P M
authors.initials: PM
authors.lastname: Mannucci
mesh_terms: D015153:Blotting, Western; D005091:Exons / Q000235:genetics; D015942:Factor VIIa / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D011486:Protein C / Q000235:genetics*; D020151:Protein C Deficiency / Q000235:genetics*; D020539:Sequence Analysis, Protein
chemical_list: D011486:Protein C; D015942:Factor VIIa