Thirty-three novel mutations in the protein C gene

We analyzed the protein C gene (PROC) with the denaturing gradient gel elec trophoresis (DGGE) scanning strategy in a series of 129 patients with suspe cted protein C (PC) deficiency (93 with low plasma PC levels and 36 with bo rderline level). Ar least one sequence variation was found in 104 of the 12 9 patients. Thirty-nine sequence variations (found in 72 patients) were alr eady reported detrimental mutations. Thirty-three were novel sequence varia tions, of which 19 (found in 25 patients) were probably detrimental. Five n ovel mutations (A1T, R9H, S11R, S12R and K193Q) were associated with qualit ative plasma PC deficiency, suggesting or confirming the functional importa nce of amino acids at these positions. This strategy confirmed the diagnosi s of inherited PC deficiency in 79/93 (84.9%) patients with low plasma PC l evels and 14/36 (38.8%) patients with borderline values. In order to explai n abnormal PC levels observed in patient, who did not carry detrimental mut ations, screening for the -1654C/T and -1641A/G PROC promoter polymorphisms known to influence plasma PC concentrations was performed. The frequency o f the CG allele associated with lower PC concentrations was slightly but no t significantly lower in 82 heterozygotes for detrimental PROC gene mutatio ns than in 36 patients with no identified detrimental mutations.