Onur Yildiz

Two candidate genes for recurrent pregnancy loss and infertility: Could ZP3 and UPK3B give us new diagnostic and therapeutic approach?

Introduction: Chromosomal indels are relatively common cytogenetic abnormalities. Nonetheless, clinical outcomes depend on the location, size and genes in deletion or duplication regions. The zona pellucida is an extracellular matrix that surrounds the oocyte and early embryo. It is composed primarily of three or four glycoproteins with various functions during fertilization and preimplantation development. The protein encoded by ZP3(Zona pellucida3) gene is a structural component of the zona pellucida and functions in primary binding and induction of the sperm acrosome reaction. UPK3B(Uroplakin 3B), a minor component of the apical plaques of mammalian urothelium that binds and dimerizes with uroplakin-1b(UPK1B), one of the major conserved urothelium membrane proteins. We herein report two cases presenting with the deletions encompassing POMZP3, UPK3B, ZP3, POM121 and POM121C genes. Case1: 25-year-old female presented to our clinic with recurrent pregnancy loss. After clinical and cytogenetic evaluation, which all of them do not feature, she was diagnosed as the deletion of POMZP3 and UPK3B genes with the array-CGH platform. (Agilent SurePrintG3 HumanCGH 60K) ‡ ‡ ‡ ‡ ‡ ‡

Comparison of the thrombophilic gene polymorphisms and recurrent pregnancy loss: Results on combined gene effect of FVLeiden, FVR2, FXIII, MTHFR(A1298C and C677T), PAI-1 4G/5G and ACE I/D genes in RPL Women from Misk/Belarus and Canakkale - Sivas/Turkey

Aim: Recurrent pregnancy loss (RPL) is a serious fertility problem with polygenic multifactorial etiology. Thrombophilia plays an important role in RPL. We compare the combined effect of the thrombophilic gene mutations as: FVL, FactorVR2, MTHFRC677T, MTHFRA1298C, PAI-15G/4G, ACEI/D and FXIII103G>T on RPL women from two different Caucasian populations (Minsk/Belarus and Canakkale Sivas/Turkey) was compared. This is the first report of thrombophilic mutations from South Slavic population of Belarusian. Methods: 1590 RPL women (830 Turkish and 760 Belarussian) were evaluated and compared in the current results. Buccal smears (for Belarussian) and peripheral blood-EDTA (for Turkish) samples were used for DNA isolation. Reverse hybridization method (for Turkish) and Real time PCR (for Turkish and Belarusian populations) were used for genotyping. Results: FVL, FVR2G/A, MTHFRA1298C are significantly frequent in Turkish RPL population than Belarusian cohort (p<0.001, p:0.002, p:0.0009 respectively) and PAI-1 5G/4G, ACE I/D, FXIII103G/T mutations are significantly frequent in Belarusian RPL population than Turkish cohort (p:0.03, p:0.001, p<0.001 respectively). MTHFR 677T allele is frequent in both populations (0.32, 0.30, p:0.2) but homozygosity is more frequent in Turkish cohort significantly, this is probably because of the frequent consanguineous marriage. ACE+PAI-1 combination is the most frequent double mutations in both cohort. The triple FVR2+ACEI/ D+FXIII103G>T mutations were same in both populations. Conclusion: Our results showed similar germ-line prothrombotic gene variations in RPL women in both populations, but the mutated FVL, FVR2G/A and MTHFRA1298G SNPs are significantly high in Turkish RPL women when compare to the Belarusian RPL women. Correspondence to: Dr. Ozturk Ozdemir, Canakkale Onsekiz Mart University, Faculty of Medicine, Department of Medical Genetics, 17100, Canakkale, Turkey, Tel: +90 286 2180018/2107, E-mail: ozdemir615@yahoo.com