Burak DURMAZ, Deniz TORUN, Salih KOZAN, Şefik GÜRAN, Muhterem BAHÇE

Tekrarlayan düşükleri olan ailede herediter mthfr c677t mutasyonunun olası rolü

Tekrarlayan düşüklerde, yaklaşık olarak %70 oranında herhangi bir neden saptanamamaktadır.Gebeliğin sorunsuz devamı için uteroplasental dolaşım çok önemlidir ve gebelik sırasındakoagülasyon faktörlerinde meydana gelen değişikliklerin, plasental damarlarda tıkanıklığa yolaçabileceğini, dolayısıyla düşük oluşumunda rol alabilecekleri düşünülmüştür. Maternalkoagülasyon faktörlerini etkileyen Faktör V Leiden G1691A, Protrombin G20210A ve MTHFRC677T mutasyonları tromboza yatkınlığı saptamada genetik test olarak kullanılmaktadır. Buyüzden maternal trombofililer ve bunların testleri klinik açıdan büyük önem taşımaktadır.Literatürde de bu parametrelerle ilgili yapılmış birçok çalışma dikkati çekmektedir. Bu olguda,ailesinde multipl düşük öyküsü olan bir çiftte karyotip analizi yapılmış ve yukarıda belirtilenmutasyonlar incelenmiştir. Kromozom analizleri normal saptanan çiftte, baba adayının MTHFRC677T mutasyonunu heterozigot olarak, anne adayının ise homozigot olarak taşıdığı saptandı. Buailede olası diğer faktörler ekarte edildiğinden, MTHFR C677T mutasyonun ailedeki düşükleriaçıklayabileceği düşünüldü ve benzer öykü ile başvuran bireylerde, belirtilen analizlerinyapılmasının tekrarlayan düşük etiyolojisini aydınlatmada yardımcı olabileceği gösterilmiştir.

The possible role of hereditary mthf r c677t mutation in a family with recurrent abortus history

The exact cause of habitual abortions can not be determined in approximately 70% of the cases.Uteroplasental circulation is very important for the ongoing pregnancy and any change in thecoagulation factors are thought to cause occlusion of the placental vessels and therefore can have arole in abortions. Mutations affecting maternal coagulation, namely Factor V Leiden G1691A,Prothrombin G20210A and MTHFR C677T are used for genetic testing to determine thepredisposition to thrombosis. For this reason, maternal thrombophilia and these tests are of greatimportance in clinical practice. In literature, many remarkable studies have been done with respectto these parameters. In this study, a couple with a history of recurrent pregnancy loss in the familywas evaluated. Karyotype analysis and the mutations mentioned above were investigated.Chromosome analysis was normal in the couple but the father was carrying heterozygote MTHFRC677T mutation and the mother had the same mutation in homozygous pattern. As the otherfactors were already ruled out in this family, we assumed that MTHFR C677T mutation mightexplain the miscarriages in the family. Performing above-mentioned mutations to other patientspresenting with the similar history may help clarify the etiology of recurrent abortions.

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1. F. Gary Cunningham, Kenneth J. Leveno, Steven L. Bloom, John C. Hauth, Dwight J. Rouse, Catherine Y. Spong Williams Obstetrics. McGraw-Hill. 22nd Ed. 2005; pp. 232-6, 1074-9.
2. Güven ESG, Güven S, İslamoğlu GA, Demir B, Günalp S. Tekrarlayan gebelik kayıplarında güncel algoritma. Hacettepe Tıp Dergisi 2006; 37: 117-23.
3. Koksal V, Baris I, Etlik O. Primer-engineered multiplex PCR-RFLP for detection of MTHFR C677T, prothrombin G20210A and factor V Leiden mutations. Exp Mol Pathol 2007; 83: 1-3.
4. Azim M, Khan AH, Khilji ZL, Pal JA, Khurshid M. Chromosomal abnormalities as a cause of recurrent abortions: a hospital experience. J Pak Med Assoc 2003; 53: 117-9.
5. Stoll C. Cytogenetic findings in 122 couples with recurrent abortions. Hum Genet 1981; 57: 101-3.
6. Robertson L, Wu O, Langhorne P, Twaddle S, Clark P, Lowe GD, Walker ID, Greaves M, Brenkel I, Regan L, Greer IA; Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thrombophilia in pregnancy: a systematic review. Br J Haematol 2006; 132: 171-96.
7. Dawood F, Mountford R, Farquharson R, Quenby S. Genetic polymorphisms on the factor V gene in women with recurrent miscarriage and acquired APCR. Hum Reprod 2007; 22: 2546-53.
8. Helley D, Besmond C, Ducrocq R, da Silva F, Guillin MC, Bezeaud A, Elion J. Polymorphism in exon 10 of the human coagulation factor V gene in a population at risk for sickle cell disease. Hum Genet 1997; 100: 245-8.
9. Rothbart H, Ohel G, Younis J, Lanir N, Brenner B. High prevalence of activated protein C resistance due to factor V leiden mutation in cases of intrauterine fetal death. J Matern Fetal Med 1999; 8: 228-30.
10. Attia FM, Mikhailidis DP, Reffat SA. Prothrombin gene G20210A mutation in acute deep venous thrombosis patients with poor response to warfarin therapy. Open Cardiovasc Med J 2009; 3: 147-51.
11. Seligsohn U, Lubetsky A. Genetic susceptibility to venous thrombosis. N Engl J Med 2001; 344: 1222-31.
12. Altomare I, Adler A, Aledort LM. The 5, 10 methylenetetrahydrofolate reductase C677T mutation and risk of fetal loss: a case series and review of the literature. Thromb J 2007; 5: 17.
13. Morales-Machín A, Borjas-Fajardo L, Quintero JM, Zabala W, Alvarez F, Delgado W, Hernández ML, Solis-Añez E, Sánchez Y, Butrón Z. C677T polymorphism of the methylentetrahydrofolate reductase gene as risk factor in women with recurrent abortion. Invest Clin 2009; 50: 327-33.
14. Laurino MY, Bennett RL, Saraiya DS, Baumeister L, Doyle DL, Leppig K, Pettersen B, Resta R, Shields L, Uhrich S, Varga EA, Raskind WH. Genetic evaluation and counseling of couples with recurrent miscarriage: recommendations of the National Society of Genetic Counselors. J Genet Couns 2005; 14: 165-81.
15. Nelen WL, Blom HJ, Steegers EA, den Heijer M, Eskes TK. Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis. Fertil Steril 2000; 74: 1196-99.
16. Foka ZJ, Lambropoulos AF, Saravelos H, Karas GB, Karavida A, Agorastos T, Zournatzi V, Makris PE, Bontis J, Kotsis A. Factor V leiden and prothrombin G20210A mutations, but not methylenetetrahydrofolate reductase C677T, are associated with recurrent miscarriages. Hum Reprod 2000; 15: 458-62.
17. Yenicesu GI, Cetin M, Ozdemir O, Cetin A, Ozen F, Yenicesu C, Yildiz C, Kocak N. A prospective case-control study analyzes 12 thrombophilic gene mutations in Turkish couples with recurrent pregnancy loss. Am J Reprod Immunol 2010; 63: 126-36.