National Academy of Sciences, Proceedings of the National Academy of Sciences, 26(118), 2021
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Significance Xeroderma pigmentosum (XP) and trichothiodystrophy (TTD), which may arise from mutations in the same genes, are distinct clinical entities with opposite skin cancer predisposition. Whereas XP is characterized by cutaneous photosensitivity and cancer proneness frequently associated with neurodegeneration, TTD shows hair anomalies, physical and mental retardation, and, in 50% of cases, cutaneous photosensitivity but no skin cancer despite the accumulation of unrepaired ultraviolet-induced DNA lesions. This study identifies a TTD-specific transcription deregulation of PTGIS (prostaglandin I 2 synthase) that results in reduced levels of prostaglandin I 2 . Reduced PTGIS is found in all TTD but not in XP patients, thus representing a biomarker for this disorder.