POLR1C and Treacher-Collins syndrome: Haploinsufficiency of Tcof1 perturbs the DNA damage response and causes the extensive apoptosis of neuroepithelial cells associated with the pathogenesis of TCS.167 In addition to TCOF1, mutations in POLR1C and POLR1D, which encode subunits of both RNA polymerase I and III, are also associated with TCS.168,169 Like TCOF1 mutations, decreased pre-rRNA transcription and number of functional 80S ribosomes were found in both polr1c- and polr1d-mutant zebrafish models of TCS.170,171 These findings highlight a causal link between ribosomal defects and the pathogenesis of TCS.