PB0972 - Germline JAK2 V617F Variant in Patient with Unprovoked Cerebral Venous Sinus Thrombosis

Background: Somatic JAK2 V617F mutations have well established roles in the pathogenesis of myeloproliferative neoplasms (MPNs), including essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Previous studies have implicated other germline variants, specifically in the kinase and pseudokinase domains, in cases of hereditary thrombocytosis. Additional research shows that somatic JAK2 V617F mutation is highly prevalent in patients with ischemic stroke, suggesting that the mutation itself may induce a prothrombotic state that goes beyond the hyperproliferation of blood cells alone.

Aims: We describe a germline JAK2 V617F variant in a male with an unprovoked cerebral venous sinus thrombosis, normal platelet count and hemoglobin and hematocrit, with negative family history of thrombotic events and MPNs.

Methods: Retrospective electronic medical records review of a Caucasian male found to harbor a germline JAK2 V617F variant.

Results: A 57-year-old Caucasian diagnosed by hereditary thrombophilia panel, including full gene analysis of the JAK2 gene, revealed a heterozygous, likely pathogenic variant, JAK2 V617F. History is positive for seemingly spontaneous occlusive right transverse and sigmoid sinus thrombosis with extension into the right internal jugular vein occurring at age 57. Personal history is negative for MPNs including essentially normal peripheral blood smear, ANA screen, comprehensive metabolic panel, C-reactive protein, and CBC with a normal platelet count and hemoglobin and hematocrit. Family history is negative for MPNs, platelet disorders, and thrombotic events.

Conclusion(s): While somatic JAK2 V617F mutations are well known causers of MPNs, the risks associated with germline JAK2 V617F mutations are not well established. This case adds to the existing literature on germline JAK2 V617F variants by documenting a patient with an atypical presentation of unprovoked cerebral venous sinus thrombosis without marked thrombocytosis or erythrocytosis. This suggests that both germline and somatic JAK2 V617F variants may be novel risk factors for cerebrovascular disease.