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Type II protein C deficiency: identification and molecular modelling of two natural mutants with low anticoagulant and normal amidolytic activity
Author(s) -
Elena M. Faioni,
José Hermida,
Ermanna Rovida,
Cristina Razzari,
Daniela Asti,
Sirous Zeinali,
Pier Mannuccio Mannucci
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.01848.x
Subject(s) - exon , mutation , proband , mutant , protein c , microbiology and biotechnology , biology , phenotype , thrombophilia , point mutation , genetics , gene , biochemistry , pregnancy
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.