Publication – Epub 2019 Nov 20.


Peter Hoeger, Veronica Kinsler, Albert Yan, John Harper, Arnold Oranje, Christine Bodemer, Margarita Larralde, David Luk, Vibhu Mendiratta, Diana Purvis


Nucleotide excision repair (NER) is the most versatile DNA repair system in humans. NER can repair a variety of bulky DNA damage including ultraviolet light‐induced DNA damage. The consequences of defective NER factors are demonstrated by the three most common but still rare autosomal recessive NER defective syndromes: xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). XP patients show severe sun sensitivity, freckling in sun exposed skin and develop skin cancers already during childhood. CS patients exhibit sun sensitivity, severe neurological abnormalities and cachectic dwarfism. Clinical features of TTD patients include sun sensitivity, ichthyosis and short brittle sulphur‐deficient hair. In contrast to XP patients, CS and TTD patients are not prone to ultraviolet light‐induced skin cancers (melanoma, squamous and basal cell carcinomas). Because the genotype–phenotype correlations are complex, these syndromes can serve as disease models for skin cancer development, neurodegeneration and epidermal cell differentiation, potentially leading to new prevention and therapeutic strategies.