XERODERMA-PIGMENTOSUM

Main clinical features: Xeroderma pigmentosum is a rare, recessive dis order clinically characterized by extreme photosensitivity, pigmented abnormalities of the skin-exposed areas, and frequent ocular and neuro logical abnormalities. Xeroderma pigmentosum syndrome is associated wi th an estimated 2000-fold increase in the risk to develop skin cancer (basal cell carcinoma, squamous cell carcinoma and melanoma). A hetero geneous disease: Skin or blood cells from Xeroderma pigmentosum patien ts are hypersensitive to killing by ultraviolet and hypermutable after ultraviolet C treatment. Cell fusion experiments based on complementa tion of repair synthesis have recognized the presence of seven Xeroder ma pigmentosum groups which exhibit various defects in the initial ste ps of the DNA nucleotide excision repair pathway. A variant Xeroderma pigmentosum form has been found to be normal in nucleotide excision re pair but abnormal in a poorly to be normal in nucleotide excision repa ir but abnormal in a poorly understood postreplication repair process. Pathophysiology: The Xeroderma pigmentosum complementation groups dif fer in terms of severity of clinical, cellular and genetic features. M olecular and biochemical studies of the Xeroderma pigmentosum syndrome have led to a better understanding of the mechanisms of ultaviolet-in duced sensitivity and the mechanism of cancer development after ultrav iolet exposure.