The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene

Background Severe protein C (PC) deficiency is a rare heritable thrombophilia leading to thromboembolic events during the neonatal period. It remains unclear how individuals with complete PC gene (PROC) defects develop or escape neonatal stroke or purpura fulminans (PF). Procedure We studied the onset of disease and the genotype of 22 PC‐deficient patients with double mutations in PROC based on our cohort (n = 12) and the previous reports (n = 10) in Japan. Results Twenty‐two patients in 20 unrelated families had 4 homozygous and 18 compound heterozygous mutations. Sixteen newborns presented with PF (n = 11, 69%), intracranial thromboembolism and hemorrhage (n = 13, 81%), or both (n = 8, 50%), with most showing a plasma PC activity of