Molecular basis for protein C hereditary deficiency.
The clinical presentation of hereditary protein C deficiency is highly variable. Homozygosity and compound heterozygosity have been linked to severe thrombotic complications early in the life. Heterozygous patients have a moderate form of the disease with deep venous thrombosis during adulthood. In the French population, we found 53 different mutations in 90 families. The amount of the protein C produced by the mutant allele as well as the genetic status partly account for the variable clinical expression. Other gene may also be involved: Arg 506 to Gln factor V mutation shows a frequency of 10 to 20% in symptomatic protein C deficient patients. Some protein C gene mutations are associated with a non functional circulating protein; most of them are located in the GLA domain and in the serine protease domain. The biochemical characterization of a few of theses variants has shown the important role of some amino acids on the activation and the mechanism of action of protein C.
Aiach
M
M
Unité INSERM 428, UFR des Sciences Pharmaceutiques et Biologiques, Université René Descartes, Paris, France.
Gandrille
S
S
D000483:Alleles; D004252:DNA Mutational Analysis; D004198:Disease Susceptibility; D005165:Factor V / Q000235:genetics; D005166:Factor V Deficiency / Q000453:epidemiology / Q000235:genetics; D005602:France / Q000453:epidemiology; D005796:Genes; D005838:Genotype; D006801:Humans; D011486:Protein C / Q000737:chemistry / Q000235:genetics; D020151:Protein C Deficiency; D017434:Protein Structure, Tertiary; D013923:Thromboembolism / Q000209:etiology* / Q000517:prevention & control
D011486:Protein C; C095381:factor V Leiden; D005165:Factor V