Xeroderma pigmentosum: from symptoms and genetics to gene-based skin therapy.

Xeroderma pigmentosum (XP) is a rare, recessively inherited genodermatosis prone to ultraviolet (UV)-induced skin neoplasms from keratinocyte origin, i.e. basal and squamous cell carcinoma. Cells from classic XP patients fail to properly eliminate UV-induced DNA lesions by the nucleotide excision repair (NER) mechanism. A variant form of XP, called XP-V suffers from faulty translesion synthesis. We review here recent data on XP gene products whose alterations affect NER and result in one of the 7 complementation groups of XP. Encouraging results of retrovirus-based genetic correction of XP keratinocytes are summarized and support realistic prospects of gene therapy for the XP-C complementation group. Copyright 2004 S. Karger AG, Basel