Öz
The methylenetetrahydrofolate reductase (MTHFR) gene encodes an enzyme called MTHFR involved in the processes of DNA methylation and chromosome segregation. MTHFR polymorphisms are associated with DNA methylation disorders including congenital malformations and chromosomal abnormalities, and various obstetrical complications such as miscarriage, fetal growth retardation, preeclampsia, preterm labor, etc. Herein, we have reported a patient with compound heterozygous MTHFR polymorphisms in whom different type of adverse pregnancy outcomes (1. blighted ovum, 2. preterm delivery, and 3. pregnancy with a fetus having anencephaly and meningocele going together with 46, XX, del (13) (q22)) were observed in her previous 3 pregnancies. She was referred to our hospital during her third pregnancy for prenatal diagnosis. Her fourth baby was born healthy at 37th gestational week after having necessary precautions. Low dose low molecular weight heparin and low-dose acetylsalicylic acid were added to patient-specific management protocol immediately after the confirmation of her fourth pregnancy. In conclusion, DNA methylation enzyme pathway disorders are associated with adverse gestational outcomes.
Anahtar Kelimeler
Methylenetetrahydrofolate reductase deficiency DNA methylation Premature birth 13q deletion syndrome neural tube defects
Kaynakça
- Recber T, Orgul G, Aydın E, et al. Metabolic infrastructure of pregnant women with methylenetetrahydrofolate reductase polymorphisms: A metabolomics analysis. Biomed Chromatogr 2020; 34:e4842.
- Turgal M, Gumruk F, Karaagaoglu E, Beksac MS. Methylenetetrahydrofolate reductase polymorphisms and pregnancy outcome. Geburtshilfe Frauenheilkund 2018; 78:871–878.
- Beksac MS, Balci S, Guvendag Guven ES, Guven S, Ozkutlu S. Complex conotruncal cardiac anomalies consecutively in three siblings from a consanguineous family possibly associated with maternal hyperhomocysteinemia. Arch Gynecol Obstet 2007; 276:547–549.
- Mudd SH, Uhlendorf BW, Freeman JM, Finkelstein JD, Shih VE. Homocystinuria associated with decreased methylenetetrahydrofolate reductase activity. Biochem Biophys Res Commun. 1972; 46(2):905–12.
- Gurbuz RH, Atilla P, Orgul G, et al. Impaired Placentation and Early Pregnancy Loss in Patients with MTHFR Polymorphisms and Type-1 Diabetes Mellitus. Fetal Pediatr Pathol. 2019; 38:376–386.
- Enciso M, Sarasa J, Xanthopoulou L, et al. Polymorphisms in the MTHFR gene influence embryo viability and the incidence of aneuploidy. Hum Genet 2016; 135:555–568.
- Lebedev IN, Ostroverkhova NV, Nikitina TV, Sukhanova NN, Nazarenko SA. Features of chromosomal abnormalities in spontaneous abortion cell culture failures detected by interphase FISH analysis. Eur J Hum Genet 2004; 12:513–520.
- Shekoohi S, Mojarrad M, Raoofian R, Ahmadzadeh S, Mirzaie S, Hassanzadeh-Nazarabadi M. Chromosomal study of couples with the history of recurrent spontaneous abortions with diagnosed blighted ovum. Int J Mol Cell Med 2013; 2:164–168.
- Lurie IW, Novikova IV, Tarletskaya OA, Lazarevich AA, Gromyko OA. Distal 13q monosomy and neural tube defects. Genet Couns 2016; 27:177–186.
- Luo J BN, Stewart JF, Sarwark JF, Charrow J, Nye JS. Neural tube defects and the 13q deletion syndrome: evidence for a critical region in 13q33-34. Am J Med Genet 2000; 91:227–230.
Öz
Metilentetrahidrofolat redüktaz (MTHFR) geni, DNA metilasyonu ve kromozom ayrılması süreçlerinde yer alan MTHFR
adı verilen bir enzimi kodlar. MTHFR polimorfizmleri, konjenital malformasyonlar ve kromozomal anomalilerini içeren
DNA metilasyon bozuklukları ve abortus, fetal büyüme geriliği, preeklampsi, erken doğum, vb. gibi çeşitli obstetrik
komplikasyonlarla ilişkilidir. Çalışmamızda compound heterozigot mutasyonu olan ve önceki üç gebeliğinde kötü obstetrik
sonuçları (1. blighted ovum, 2. preterm doğum ve 3. anensefali ve meningoseli, 46, XX, del (13) (q22) ile birlikte seyreden
bir fetus ile gebelik) olan bir hasta değerlendirilmiştir. Hastanın dördüncü bebeği gerekli önlemleri aldıktan sonra 37.
gebelik haftasında sağlıklı doğdu. Dördüncü gebeliğin doğrulanması takiben düşük doz düşük moleküler ağırlıklı heparin
ve düşük doz asetilsalisilik asit hastaya özgü yönetim protokolü çerçevesinde başlandı. Sonuç olarak, DNA metilasyon
enzimi yolu bozuklukları, olumsuz gebelik sonuçları ile ilişkilidir.
Anahtar Kelimeler
DNA metilasyonu 13q delesyon sendromu Metilentetrahidrofolat redüktaz polimorfizmleri erken doğum 13q delesyon sendromu nöral tüp defektleri
Kaynakça
- Recber T, Orgul G, Aydın E, et al. Metabolic infrastructure of pregnant women with methylenetetrahydrofolate reductase polymorphisms: A metabolomics analysis. Biomed Chromatogr 2020; 34:e4842.
- Turgal M, Gumruk F, Karaagaoglu E, Beksac MS. Methylenetetrahydrofolate reductase polymorphisms and pregnancy outcome. Geburtshilfe Frauenheilkund 2018; 78:871–878.
- Beksac MS, Balci S, Guvendag Guven ES, Guven S, Ozkutlu S. Complex conotruncal cardiac anomalies consecutively in three siblings from a consanguineous family possibly associated with maternal hyperhomocysteinemia. Arch Gynecol Obstet 2007; 276:547–549.
- Mudd SH, Uhlendorf BW, Freeman JM, Finkelstein JD, Shih VE. Homocystinuria associated with decreased methylenetetrahydrofolate reductase activity. Biochem Biophys Res Commun. 1972; 46(2):905–12.
- Gurbuz RH, Atilla P, Orgul G, et al. Impaired Placentation and Early Pregnancy Loss in Patients with MTHFR Polymorphisms and Type-1 Diabetes Mellitus. Fetal Pediatr Pathol. 2019; 38:376–386.
- Enciso M, Sarasa J, Xanthopoulou L, et al. Polymorphisms in the MTHFR gene influence embryo viability and the incidence of aneuploidy. Hum Genet 2016; 135:555–568.
- Lebedev IN, Ostroverkhova NV, Nikitina TV, Sukhanova NN, Nazarenko SA. Features of chromosomal abnormalities in spontaneous abortion cell culture failures detected by interphase FISH analysis. Eur J Hum Genet 2004; 12:513–520.
- Shekoohi S, Mojarrad M, Raoofian R, Ahmadzadeh S, Mirzaie S, Hassanzadeh-Nazarabadi M. Chromosomal study of couples with the history of recurrent spontaneous abortions with diagnosed blighted ovum. Int J Mol Cell Med 2013; 2:164–168.
- Lurie IW, Novikova IV, Tarletskaya OA, Lazarevich AA, Gromyko OA. Distal 13q monosomy and neural tube defects. Genet Couns 2016; 27:177–186.
- Luo J BN, Stewart JF, Sarwark JF, Charrow J, Nye JS. Neural tube defects and the 13q deletion syndrome: evidence for a critical region in 13q33-34. Am J Med Genet 2000; 91:227–230.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Kadın Hastalıkları ve Doğum |
| Bölüm | Olgu Sunumu |
| Yazarlar | |
| Yayımlanma Tarihi | 28 Aralık 2020 |
| Kabul Tarihi | 24 Aralık 2020 |
| Yayımlandığı Sayı | Yıl 2020 Cilt: 2 Sayı: 4 |
