In contrast, loss-of-function mutations in TC-NER components (most prominently CSA/ERCC8 and CSB/ERCC6) do not lead to cancer but rather to diseases characterised by pronounced neurological features and segmental degeneration, such as Cockayne syndrome (CS) and an even more severe cerebro-oculo-facio-skeletal syndrome (COFS). Here, ERCC6 is linked to Cowden syndrome 1.