Interestingly, the intrinsic pro-apoptotic genes implicated in exencephaly in mice TP53 [43], APAF1 [44], CASP9 [45] and CASP3 [46] harbored 16 PDRVs in human NTD cases, considerably increased relative to controls (16/355 vs. 1/225, P = 0.0044, two-sided Fisher’s exact test) (Fig. 2b). This evidence concerns the gene APAF1 and neural tube defect.