While the precise mechanism responsible for DNA hypomethylation in AGS remains to be elucidated, it is worth noting that defects in TREX1, RNase H2, and SAMHD1 all trigger the DNA damage response and are associated with increased genomic instability (Yang et al., 2007; Reijns et al., 2012; Clifford et al., 2014; Kretschmer et al., 2015). The gene discussed is TREX1; the disease is Aicardi-Goutieres syndrome.