Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype

Abstract

Background/Aim. Ischemic stroke is a heterogeneous disorder caused by several genetic and environmental risk factors. It was suggested that coagulation disorders cause 1-4% of cases with ischemic stroke, especially in patients with early-onset of ischemic stroke. Case report. Here, we describe a case of patient who developed an unprovoked ishemic stroke in young adult. Biochemical, immunological and thrombophilia screening, as well DNA sequencing were performed in order to reveal molecular pathology underlying stroke of patient. Thrombophilia testing showed that patient was homozygous carrier for PAI-1 4G/5G and MTHFR C677T mutations. Additional genetic analysis revealed the presence of recently reported FII c.1824C>T gene variant, which is located in the last exon of prothrombin gene and previously shown to cause hyperprothrombinemia, hypofibrinolysis and altered fibrin clot phenotype. Conclusion. Our results suggest that newly reported FII c.1824C>T gene variant might have synergistic effect with PAI 4G/4G and MTHFR 677TT genotype in formation of altered fibrin clot phenotype characterized by thin, densely packed fibrin fibers, which makes clot less susceptible to fibrinolysis and greatly increases the risk for early ischemic stroke onset.