We found that the MTHFR C677T genotype/low folate diet combination was significantly associated with LINE-1 hypomethylation in mothers with children with DS who developed septal defects, and our previous study showed that significant LINE-1 hypomethylation (compared to controls) in the mothers of children with DS was itself significantly associated with the MTHFR C677T genotype/diet combination (Božović et al., 2015). Here, MTHFR is linked to Abnormal cardiac septum morphology.