One important gene that is involved in this metabolism is DHFR, which encodes the enzyme responsible for reducing folic acid in THF.9 A common polymorphism in this gene, 19-bp deletion polymorphism in intron-1, has been correlated with modulation of the maternal risk of neural tube defects (NTDs),10,11 and of the concentrations of the metabolites involved in the folate pathway.9,13,25. Here, DHFR is linked to isolated spina bifida.