C9orf72 and amyotrophic lateral sclerosis: Although the G4C2 expansion does cause a decrease in C9ORF72 mRNA, it is not clear that this leads to loss of the C9ORF72 protein and no null alleles or missense mutations in C9ORF72 have been identified in ALS or FTD cases to support the loss of C9ORF72 protein function hypothesis.