Identification of Novel Mutations in Amniotic Fluid Derived Stem Cells Collected from the Mothers Having Case of Neural Tube Defects

Abstract

Neural tube defects (NTDs) are severe congenital malformations of central nervous system that have high prevalence with severe consequences. The etiology of NTDs involves interactions of both genetic and epigenetic factors and their complex interactions with stems cells during organogenesis. Despite of recent advances, there has been limited progress in delineating the molecular basis of NTDs that can pave way for prevention, diagnostics and therapeutics. We have previously identified a role for stem cell markers Oct 4, Sox 2 and Nanog 3 in neural tube defect affected pregnancies. In the present report we identified mutations in stem cell pluripotency markers from amniotic fluid derived stem cells isolated from women with NTD affected pregnancy. Oct 4 and Nanog 3 were studied to find a correlation with the disease and its severity. Interestingly, sequence based DNA analysis revealed two different forms of nucleotide changes that were observed in different clinical conditions of NTDs. The mutation in Oct 4 at position 183 G →T and in the sequence of Nanog 3 at ⁶³CAAAAA ACA⁷² to ³⁸ACAGTCTCT⁴⁷ appears in the cases of anencephaly and meningomyelocele respectively in comparison to control. These findings suggest that these mutational spectra might be responsible for the alterations in the developmental process during embryogenesis leading to NTDs.