Definite diagnosis in Japanese patients with protein C deficiency by identification of causative PROC mutations

Excerpt

Protein C is a vitamin K-dependent plasma glycoprotein that functions as an important regulator of blood coagulation, and its deficiency is known to be a risk factor for thrombosis [1]. Congenital protein C deficiency is an autosomally inherited disorder, and has been classified into 2 types: a quantitative deficiency (type I), and qualitative deficiency (type II) [2]. Heterozygous patients with inherited protein C deficiency are mildly affected, and are either symptomatic (1 in 16,000 of the general population [3]) or asymptomatic (1 in 500 of the healthy population [4]). Thus, protein C deficiency in itself is thought to be a relatively mild risk factor for thromboembolism, and it is suggested that thrombosis-prone protein C deficient families might carry additional genetic factors that increase the risk, such as FV Leiden mutation and prothrombin 20210G > A mutation in Caucasian populations [5]. Severe congenital protein C deficiency is a much rarer disease, most often caused by a homozygous (or compound heterozygous) protein C gene (PROC) mutation(s). Some homozygous subjects develop purpura fulminans or skin necrosis and intravascular disseminated coagulation at birth [6‐8], while heterozygous deficiency predisposes to venous thrombosis in adulthood. This clinical heterogeneity could reflect a variety of molecular mechanisms. …