C9orf72 and amyotrophic lateral sclerosis: Our findings are consistent with recent findings in which the multistep model of ALS20 was applied to three known genetic causes of ALS: mutation in SOD1, mutation in TARDBP (coding for TDP43) and pathological expansion of a hexanucleotide repeat in the C9orf72 gene.21 These gene variants account for more than one step in the pathological process leading to ALS, leaving fewer risk factors to encounter before onset and therefore making a younger age of onset more likely.