ERCC6 and Cowden syndrome 1: CS arises primarily from pathogenic variants in ERCC6 (CSB) and ERCC8 (CSA), which disrupt transcription-coupled nucleotide excision repair (TC-NER), impairing DNA damage response and driving multisystem pathology (Pascucci et al., 2018; Pines et al., 2018; Cordisco et al., 2019; Carnie et al., 2024).