A new hereditary PROS1 gene mutation caused isolated cortical venous thrombosis

Protein S deficiency is a rare inherited disease. We report the case of a young man who unexpectedly developed isolated cortical vein thrombosis (ICoVT) associated with a novel PROS1 mutation.

Clinical symptoms were recorded, and physical examinations conducted. Comprehensive laboratory tests included routine coagulation function tests, protein C activity, and antithrombin III levels. Advanced imaging techniques, such as magnetic resonance imaging (MRI), magnetic resonance venography (MRV), and computed tomography angiography (CTA) were employed. We also performed genetic analysis on the patient and his parents.

The patient presented with headaches and paroxysmal convulsions without identifiable triggers. Physical examinations and routine coagulation tests were generally normal, except for a markedly reduced protein S activity at 21.2 %. MRI scans revealed right parietal cerebral hemorrhage and thickening of the cortical vein, characterized by high T1-weighted Imaging and low T2-weighted Imaging and Fluid-Attenuated Inversion Recovery signals. CTA and Doppler ultrasound of the lower limbs showed no abnormalities. Family history revealed that his father had suffered from multiple venous thromboses. Genetic testing identified a missense mutation (c.1912G>T p.Gly638Cys) in both the patient and his father, along with a duplication of approximately 403.6 kb on chromosome 3q26.32-33 in the patient.

This case highlights a novel PROS1 missense mutation and its significant role in development of cortical venous thrombosis. It provides a new insight into the genetic basis of autosomal dominant thrombophilia associated with protein S deficiency (THPH5).