title: A novel thrombomodulin gene mutation in a patient suffering from sagittal sinus thrombosis.
abstract: Thrombomodulin is an endothelial cell membrane glycoprotein that promotes protein C activation. It has been clearly demonstrated that the anticoagulant functions of the protein C system are important in the prevention of thromboembolic disease. Patients with protein C or protein S deficiency and/or resistance to activated protein C (APC resistance) are at higher risk for developing thromboembolic disease. The first mutation in the thrombomodulin gene was discovered in an American patient suffering from pulmonary embolism at the age of 45 (Ohlin and Marlar 1995). Here we report a case of sagittal sinus thrombosis in a 42-year-old Swedish woman. She was found to carry a heterozygous point mutation changing G127 to A, predicting an Ala25 to a Thr change in the mature thrombomodulin protein. This mutation was also found in her 16-year-old daughter, who so far has not suffered from any thrombotic events. The patient had no other detectable prothrombotic genetic defects associated with the coagulation system. This case supports the hypothesis of an association between mutations in the thrombomodulin gene and venous thrombosis.
authors.affiliation: Department of Laboratory Medicine, University of Lund, University Hospital, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Norlund
authors.forename: B
authors.initials: B
authors.lastname: Zöller
authors.forename: A K
authors.initials: AK
authors.lastname: Ohlin
mesh_terms: D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D004198:Disease Susceptibility; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011486:Protein C / Q000378:metabolism; D011655:Pulmonary Embolism / Q000209:etiology; D012851:Sinus Thrombosis, Intracranial / Q000235:genetics*; D018180:Thrombomodulin / Q000235:genetics*; D019851:Thrombophilia / Q000235:genetics*; D013924:Thrombophlebitis / Q000209:etiology
chemical_list: D011486:Protein C; D018180:Thrombomodulin