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

  • Iva Pruner University of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Belgrade, Serbia
  • Evica Dinčić University of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia; Military Medical Academy, Clinic for Neurology, Belgrade, Serbia
  • Maja Gvozdenov University of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Belgrade, Serbia
  • Branko Tomić University of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Belgrade, Serbia
  • Mirjana Kovač University of Belgrade, Faculty of Medicine, Belgrade, Serbia
  • Valentina Djordjević University of Belgrade, Faculty of Medicine, Belgrade, Serbia
Keywords: fibrin;, genes;, genetic variation;, genotype;, sequence analysis, dna;, stroke;, thrombophilia.

Abstract


Introduction. Ischemic stroke (IS) is a heterogeneous disorder caused by several genetic and environmental risk factors. It was suggested that coagulation disorders cause 1-4% of cases with IS, especially in patients with early onset of IS. Case report. We describe a case of a young adult male who developed an unprovoked IS. Biochemical, immunological, and thrombophilia screening, as well as DNA sequencing, were performed in order to reveal molecular pathology underlying the stroke of the patient. Thrombophilia testing showed that patient was a homozygous carrier for PAI-1 4G/5G and MTHFR C677T mutations. Additional genetic analysis revealed the presence of the recently reported F2 c.1824C>T gene variant, located in the last exon of the prothrombin gene and has previously been shown to cause hyperprothrombinemia, hypofibrinolysis, and altered fibrin clot phenotype. Conclusion. Our results suggest that the newly reported F2 c.1824C>T gene variant might have a synergistic effect with PAI 4G/4G and MTHFR 677TT genotype in the 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.

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Published
2022/12/02
Section
Case report