IRES mutations can alter protein expression and cause disease. For example, the 5′UTR of the proto-oncogene c-MYC contains an IRES and, in patients with multiple myeloma, a C>T substitution within the IRES causes increased synthesis of c-MYC protein by favouring the binding of two ITAFs, Y-box binding protein 1 (YB-1) and polypyrimidine tract-binding protein 1 (PTB-1).36 Another example is represented by a mutation in the IRES of the connexin-32 gene, which abolishes translation of the corresponding mRNA in nerve cells, leading to Charcot-Marie-Tooth disease, a neurodegenerative disorder.37
