Compound heterozygous mutations in the PROS1 gene responsible for quantitative and qualitative protein S deficiency

Abstract

Protein S (PS) is a vitamin K-dependent plasma glycoprotein, which plays an important role in the blood anticoagulant system. The PS gene (PROS1) spans some 80 kb of genomic DNA, composed of 15 exons and 14 introns, and is closely linked to a highly homologous pseudogene (PROS2), whose sequence is 96% identical to that of PROS1 [1]. Congenital PS deficiency caused by PROS1 mutations is associated with an increased risk of thromboembolic disease. In this study, we investigated the molecular basis of a patient with both quantitative and qualitative PS deficiency. A 69-year-old man had a medical examination in our hospital because of progressive bilateral leg pain and swelling. He was diagnosed with deep vein thrombosis (DVT) based on the venographs of the legs. Laboratory tests showed normal values of platelet count, prothrombin time, activated partial thromboplastin time, ATIII activity and protein C activity. Test results for lupus anticoagulant and anti-cardiolipin b2GPI antibody were negative. Total PS antigen, free-PS antigen and PS activity levels were 49.0% (normal range 65‐135%), 26.7% (60‐150%) and 10% (60‐150%), respectively. From these findings, he was diagnosed as having PS deficiency.