C9orf72 and amyotrophic lateral sclerosis: When mutations in C9ORF72 were discovered in familial cases of FTD and ALS in 2011, three independent teams provided evidence that the disease is caused by a (G4C2)n HRE G4C2 in the first intronic region of C9ORF72 (Figure 2B; DeJesus-Hernandez et al., 2011; Renton et al., 2011; Gijselinck et al., 2016).