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.

Type II protein C deficiency: identification and molecular modelling of two natural mutants with low anticoagulant and normal amidolytic activity / E. Faioni, J. Hermida, E. Rovida, C. Razzari, D. Asti, S. Zeinali, P. Mannucci. - In: BRITISH JOURNAL OF HAEMATOLOGY. - ISSN 0007-1048. - 108:2(2000), pp. 265-271.

Type II protein C deficiency: identification and molecular modelling of two natural mutants with low anticoagulant and normal amidolytic activity

E. Faioni
Primo
;
2000

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.
Catalytic site; Gla domain; Na+ binding site; Protein C deficiency; Venous thromboembolism
Settore MED/09 - Medicina Interna
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/185972
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