Novel Genetic Variants of the PROS1 Protein S Gene of an Individual with Protein S Deficiency

Introduction: Human Protein S (PS) is an anticoagulant essential for maintaining hemostasis. Although rare, PS deficiency can cause life-threatening thrombophilia. We found novel genetic variations in the PROS1 gene of a 46-year-old woman who was diagnosed with PS deficiency. We hypothesize how the mutations affect PS level and function. Materials and Methods: Citrated plasma was isolated from the patient’s blood. Biochemical analyses were conducted via activated partial thromboplastin time and thrombin generation assays with the addition of various concentrations of PS. Immunoblotting and ELISA were used to measure levels of PS in the woman’s plasma. We sequenced the entire PROS1 gene on chromosome 3 for two control samples and the individual’s sample. Results: We found two novel deletions and a novel insertion in the PROS1 gene of the patient. The deletions and insertion were predicted to activate cryptic splice acceptor and donor splice sites, respectively. In addition, the patient had alteration in whole blood coagulation parameters, including a prolonged aPTT and decreased plasma PS level. Conclusion: The genetic alterations in the patient’s PROS1 gene are predicted to cause inappropriate splicing of PS pre-mRNA that likely contributes to the Type I PS deficiency and abnormal coagulation properties of the study patient.