The presence of pathogenic hexanucleotide G4C2 repeats expansion (pHRE) in intron 1, between non-coding exons 1a and 1b of the gene C9orf72, leads to the development of C9-ALS/FTD by loss-of-function and/or toxic gain-of-function mechanisms. Here, C9 is linked to amyotrophic lateral sclerosis.