MLH1 and folate deficiency: Liu et al. studied the genomic instability in human fetuses with NTDs under folate deficiency; the results demonstrated that the total positive rate of MSI in the NTDs group was 46% (23 of 50 NTD patients) and hMLH1 promoter demonstrated two specific methylation patterns at “4,5 CpG” sites in the target region, which were a 180-bp fragment upstream from exon-1 of hMLH1 (−271 to −92 bp, containing 11 CpG sites) in some NTD samples [76].