Xeroderma Pigmentosum: Variants with Normal Dna Repair and Normal Sensitivity to Ultraviolet Light

Abstract

The subjects are three patients with distinct symptoms of xeroderma pigmentosum (XP) in which the cultured fibroblasts are different from those usually found in this disease. Ordinarily, XP fibroblasts are extremely sensitive to ultraviolet (UV) light and perform reduced amounts of repair replication during the repair of damage to DNA. Cells from the three new variants of XP are indistinguishable from normal cells: their sensitivity to UV light is normal and they perform normal amounts of repair replication. Because of this normal sensitivity, it is unlikely that a defect in any DNA repair mechanism is present in these cases; in microorganisms defects in repair are invariably associated with increased sensitivity. These results imply that a minority of those cases which are clinically diagnosed as XP constitute a biochemically distinct condition, and possible relationships previously inferred between DNA repair and carcinogenesis must be cautiously evaluated. Cells from parents (heterozygotes) of an XP patient with reduced DNA repair also show reduced DNA repair when they are subjected to high doses of UV light which presumably exceed the repair capacity of the partial (heterozygous) repair defect.