Xeroderma pigmentosum, cockayne syndrome and trichothiodystrophy: Sun sensitivity, DNA repair defects and skin cancer

Abstract

Xeroderma pigmentosum (XP) is a rare, autosomal recessive disease1 with a combination of clinical, cellular and molecular features that initially generated an intellectually satisfying and simple association between defects in DNA repair, increased mutability and cancer proneness. As the study of XP patients has proceeded, however, interesting anomalies and unanticipated complexities have been uncovered. In particular, as a consequence of using XP as a model, two other rare but not cancerprone, autosomal recessive diseases, Cockayne syndrome (CS) and trichothiodystrophy (TTD) have extended the apparent relationship of DNA repair defects to a wide spectrum of associated clinical features.1 The relationship between the three conditions is complex – there are a few individuals with the features of both XP and CS, and mutations in one of the XP genes can give rise to individuals with XP, TTD, cerebro-oculofacioskeletal syndrome (COFS), XP with CS, or XP with TTD. In order to understand the relationship between DNA damage/repair and cancer revealed in XP, it is necessary to study all three conditions at the clinical, cellular and molecular Comprehensive reviews of the clinical characteristics of XP are available.1,2 The individuals are sun sensitive, and this is coupled with an abnormal erythemal response.