In our previous study, we observed a significant decrease in D-loop region methylation levels in both presymptomatic and symptomatic SOD1 mutant carriers, suggesting that D-loop methylation alteration is an early event at least in individuals with ALS-linked SOD1 mutations and precedes the onset of the disease symptoms and likely acting as a compensatory mechanism to counteract SOD1 deficiency in those individuals [23]. The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.