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

Introduction. Ischemic stroke (IS) is a heterogeneous dis-order 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...

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Main Authors: Pruner Iva, Dinčić Evica, Gvozdenov Maja, Tomić Branko, Kovač Mirjana, Đorđević Valentina
Format: Article
Language:English
Published: Ministry of Defence of the Republic of Serbia, University of Defence, Belgrade 2022-01-01
Series:Vojnosanitetski Pregled
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Online Access:http://www.doiserbia.nb.rs/img/doi/0042-8450/2022/0042-84502100066P.pdf
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author Pruner Iva
Dinčić Evica
Gvozdenov Maja
Tomić Branko
Kovač Mirjana
Đorđević Valentina
author_facet Pruner Iva
Dinčić Evica
Gvozdenov Maja
Tomić Branko
Kovač Mirjana
Đorđević Valentina
author_sort Pruner Iva
collection DOAJ
description Introduction. Ischemic stroke (IS) is a heterogeneous dis-order 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 pro-thrombin gene and has previously been shown to cause hy-perprothrombinemia, 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 in-creases the risk for early ischemic stroke onset.
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institution Kabale University
issn 0042-8450
2406-0720
language English
publishDate 2022-01-01
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series Vojnosanitetski Pregled
spelling doaj-art-05bfc9d3f296427abd72fd78577bb2942025-08-20T03:54:16ZengMinistry of Defence of the Republic of Serbia, University of Defence, BelgradeVojnosanitetski Pregled0042-84502406-07202022-01-0179101039104310.2298/VSP210323066P0042-84502100066PEarly-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotypePruner Iva0https://orcid.org/0000-0002-8803-5907Dinčić Evica1Gvozdenov Maja2https://orcid.org/0000-0001-9856-2834Tomić Branko3https://orcid.org/0000-0002-5875-0619Kovač Mirjana4https://orcid.org/0000-0001-6676-0561Đorđević Valentina5University of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Belgrade, SerbiaUniversity of Defence, Faculty of Medicine of the Military Medical Academy, Belgrade, Serbia + Military Medical Academy, Clinic for Neurology, Belgrade, SerbiaUniversity of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Belgrade, SerbiaUniversity of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Belgrade, SerbiaUniversity of Belgrade, Faculty of Medicine, Belgrade, Serbia + Blood Transfusion Institute of Serbia, Hemostasis Department, Belgrade, SerbiaUniversity of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Belgrade, SerbiaIntroduction. Ischemic stroke (IS) is a heterogeneous dis-order 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 pro-thrombin gene and has previously been shown to cause hy-perprothrombinemia, 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 in-creases the risk for early ischemic stroke onset.http://www.doiserbia.nb.rs/img/doi/0042-8450/2022/0042-84502100066P.pdffibringenesgenetic variationgenotypesequence analysis, dnastrokethrombophilia
spellingShingle Pruner Iva
Dinčić Evica
Gvozdenov Maja
Tomić Branko
Kovač Mirjana
Đorđević Valentina
Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype
Vojnosanitetski Pregled
fibrin
genes
genetic variation
genotype
sequence analysis, dna
stroke
thrombophilia
title Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype
title_full Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype
title_fullStr Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype
title_full_unstemmed Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype
title_short Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype
title_sort early onset ischaemic stroke in a patient with the novel f2 c 1824c t gene variant and pai 1 4g 4g mthfr 677tt genotype
topic fibrin
genes
genetic variation
genotype
sequence analysis, dna
stroke
thrombophilia
url http://www.doiserbia.nb.rs/img/doi/0042-8450/2022/0042-84502100066P.pdf
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