It is speculated that this may reduce the methylation capacity available for other key cellular needs.3 In the splotch (Sp2H; Pax3 mutant) strain, female susceptibility to exencephaly is exacerbated by dietary folate deficiency to a greater extent than in males.37 While the aetiology of human NTDs is more complex than in single-gene models, if such a scenario occurs in some human NTDs, then it might be predicted that an overall increase in population-level folate status may have a greater effect on NTDs in women than in men. Here, PAX3 is linked to folate deficiency.