DNA Repair Disorders with Cutaneous Features

Abstract

Abstract The human genome is continually being damaged by a variety of sources (such as reactive oxygen species and ultraviolet and ionizing radiation). Cells have evolved a number of complex pathways (nucleotide excision repair, double strand break repair and mismatch repair) to recognize and repair this damage in actively transcribed genes. Defects in these pathways result in a number of disorders, many with skin involvement, commonly photosensitivity, cancer and premature ageing. Xeroderma pigmentosum (XP), Cockayne syndrome and trichothiodystrophy are caused by defects in the nucleotide excision repair. All three syndromes can show photosensitivity because of an inability to repair UV radiation‐induced DNA damage. However, they are clinically very heterogeneous and only patients with XP have an increased risk of skin cancer. Early accurate diagnosis, based on clinical features, assessment of DNA repair and genetic analysis, can significantly improve morbidity and mortality from skin cancers, and also enables appropriate genetic counselling and prenatal diagnosis.