Furthermore, we recently investigated ALS families with SOD1, C9orf72, FUS, or TARDBP pathogenetic variants, observing that the methylation levels of the mitochondrial D-loop region were significantly decreased only in peripheral blood lymphocytes of carriers of ALS-linked SOD1 variants, either ALS patients or pre-symptomatic carriers. Here, TARDBP is linked to amyotrophic lateral sclerosis.