Protein S deficiency: a database of mutations - summary of the first update

Protein S is a vitamin K dependent protein whose inherited deficiency is a well recognized risk factor for venous thrombosis. Its role is to act as activated protein C cofactor in factor Va and VIIIa proteolysis, thus restricting thrombin generation. Its gene lies on chromosome 3, at position 3p11.1-q11.2, and its structural organization has been described. Elucidation of the gene defects responsible for protein S deficiency is proceeding rapidly. A first record of identified mutations was undertaken in 1996 under the auspices of the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee (ISTH SSC) and was published in 1997 (Thromb Haemost 1997; 77: 1201-14). This first database reported mutations identified in 126 protein S-deficient subjects postulated to be detrimental, and 19 mutations that were considered as neutral polymorphisms. The classification proposed by Bertina at the subcommittee meeting in 1991 was used to classify the mutations according to the phenotype observed in deficient subjects, that is type I when both free and total PS antigen levels were decreased, type III when free PS levels were decreased with normal total PS antigen levels, and type II when cofactor activity of PS was decreased while total and free antigen levels were within the normal ranges