TY  - JOUR
AU  - Pruner, Iva
AU  - Dinčić, Evica
AU  - Gvozdenov, Maja
AU  - Tomić, Branko
AU  - Kovač, Mirjana
AU  - Đorđević, Valentina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1646
AB  - 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.
AB  - Ishemijski moždani udar (IMU) je heterogeni poremećaj
koji može biti uzrokovan genetskim faktorima rizika i faktorima
sredine. Poremećaji koagulacije mogu biti uzročnici u 1-4%
slučajeva IMU, naročito kod bolesnika kod kojih se IMU dogodi u
mlađem životnom dobu. Prikaz bolesnika. Prikazan je slučaj
bolesnika koji je u mlađem životnom dobu razvio IMU
nepoznatog uzroka. Urađeni su biohemijski, imunološki i testovi za
trombofiliju kao i sekvenciranje DNK sa ciljem da se utvrdi
molekularna patologija koja je mogla biti u osnovi moždanog udara
kod tog bolesnika. Testovima za trombofiliju utvrđeno je da je
bolesnik homozigotni nosilac mutacija PAI-1 4G/5G i MTHFR
C677T. Dodatnom genetičkom analizom otkriveno je prisustvo
nedavno opisane F2 c.1824C>T genske varijante, koja se nalazi u
poslednjem egzonu gena za protrombin i za koju je prethodno
pokazano da izaziva hiperprotrombinemiju, hipofibrinolizu i
izmenjeni fenotip fibrinskog ugruška. Zaključak. Naši rezultati
ukazuju na to da bi nova F2 c.1824C>T genska varijanta mogla
imati sinergistički efekat sa PAI 4G/4G i MTHFR 677TT
genotipom u nastanku fibrinskog ugruška sa izmenjenim
fenotipom, koji se odlikuje tankim, gusto upakovanim fibrinskim
vlaknima, što čini ugrušak manje podložnim fibrinolizi i povećava
rizik od nastanka IMU u ranijem životnom dobu.
T2  - Vojnosanitetski pregled
T2  - Vojnosanitetski pregled
T1  - Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype
EP  - 1043
IS  - 10
SP  - 1039
VL  - 79
DO  - doi.org/10.2298/VSP210323066P
ER  - 

@article{
author = "Pruner, Iva and Dinčić, Evica and Gvozdenov, Maja and Tomić, Branko and Kovač, Mirjana and Đorđević, Valentina",
year = "2022",
abstract = "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., Ishemijski moždani udar (IMU) je heterogeni poremećaj
koji može biti uzrokovan genetskim faktorima rizika i faktorima
sredine. Poremećaji koagulacije mogu biti uzročnici u 1-4%
slučajeva IMU, naročito kod bolesnika kod kojih se IMU dogodi u
mlađem životnom dobu. Prikaz bolesnika. Prikazan je slučaj
bolesnika koji je u mlađem životnom dobu razvio IMU
nepoznatog uzroka. Urađeni su biohemijski, imunološki i testovi za
trombofiliju kao i sekvenciranje DNK sa ciljem da se utvrdi
molekularna patologija koja je mogla biti u osnovi moždanog udara
kod tog bolesnika. Testovima za trombofiliju utvrđeno je da je
bolesnik homozigotni nosilac mutacija PAI-1 4G/5G i MTHFR
C677T. Dodatnom genetičkom analizom otkriveno je prisustvo
nedavno opisane F2 c.1824C>T genske varijante, koja se nalazi u
poslednjem egzonu gena za protrombin i za koju je prethodno
pokazano da izaziva hiperprotrombinemiju, hipofibrinolizu i
izmenjeni fenotip fibrinskog ugruška. Zaključak. Naši rezultati
ukazuju na to da bi nova F2 c.1824C>T genska varijanta mogla
imati sinergistički efekat sa PAI 4G/4G i MTHFR 677TT
genotipom u nastanku fibrinskog ugruška sa izmenjenim
fenotipom, koji se odlikuje tankim, gusto upakovanim fibrinskim
vlaknima, što čini ugrušak manje podložnim fibrinolizi i povećava
rizik od nastanka IMU u ranijem životnom dobu.",
journal = "Vojnosanitetski pregled, Vojnosanitetski pregled",
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",
pages = "1043-1039",
number = "10",
volume = "79",
doi = "doi.org/10.2298/VSP210323066P"
}

Pruner, I., Dinčić, E., Gvozdenov, M., Tomić, B., Kovač, M.,& Đorđević, V.. (2022). Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype. in Vojnosanitetski pregled, 79(10), 1039-1043.
https://doi.org/doi.org/10.2298/VSP210323066P

Pruner I, Dinčić E, Gvozdenov M, Tomić B, Kovač M, Đorđević V. Early-onset ischaemic stroke in a patient with the novel F2 c.1824C>T gene variant and PAI-1 4G/4G, MTHFR 677TT genotype. in Vojnosanitetski pregled. 2022;79(10):1039-1043.
doi:doi.org/10.2298/VSP210323066P .

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" in Vojnosanitetski pregled, 79, no. 10 (2022):1039-1043,
https://doi.org/doi.org/10.2298/VSP210323066P . .