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Anencephaly and myelomeningocele are the 2 most common forms of neural tube defects (NTDs). During embryogenesis large numbers of extrinsic and intrinsic factors are responsible for the closing of the neural tube. "Stem cells" maintain the pluripotency during differentiation of 3 germ layers, including the neural ectoderm. We examined the role of Oct4, Nanog3, and Sox2 genes in the etiopathology of NTDs in an eastern Indian population using PCR-based DNA analysis. The highest frequency (16%) of complete loss of the Sox2 gene was found in NTDs. The highest frequency (48%) of overexpression (upregulation) was found for Nanog3, while 40% was observed for Oct4 and Sox2. The odds ratio for cases versus controls was from 0.132 at 95% confidence interval = 0.005-1.298 for Nanog3 to 2.316 (0.424-13.812) for Oct4. The highest frequency (77%) of overexpression for Nanog3 and Sox2 was observed in encephalocele and anencephalic patients, while in the comparison of regional variation, i.e., cephalic to caudal regions of NTDs, the highest frequency of downregulation (regression) of Nanog3 and Sox2 was found in lumbosacral myelomeningocele patients. However, cervical myelomeningocele patients had the highest frequency of overexpression in all 3 genes, suggesting that the mutational spectra of stem cells influence the cells of the neural crest in NTDs.

Genetic diversity of stem cells and their functional impact on the development of neural tube defects in Eastern population of India