A newly identified patient with clinical xeroderma pigmentosum phenotype has a non-sense mutation in the DDB2 gene and incomplete repair in (6-4) photoproducts

We report here a patient (Ops1) with clinical photosensitivity, including p igmented or depigmented macules and patches, and multiple skin neoplasias ( malignant melanomas, basal cell carcinomas, and squamous cell carcinomas in situ) in sun-exposed areas. These clinical features are reminiscent of xer oderma pigmentosum. As cells from Ops1 showed normal levels in DNA repair s ynthesis in vivo (unscheduled DNA synthesis and recovery of RNA synthesis a fter ultraviolet irradiation), we performed a postreplication repair assay and recovery of replicative DNA synthesis after ultraviolet irradiation to investigate if Ops1 cells belonged to a xeroderma pigmentosum variant patte rn. Ops1 cells were normal, but there was an incomplete pattern repair in ( 6-4) photoproducts in contrast to a normal pattern repair in cis-syn cyclob utane pyrimidine dimers by repair kinetics using the enzyme-linked immunoso rbent assay. Moreover, Ops1 cells were defective in a damage-specific DNA b inding protein and carried a non-sense mutation in the DDB2 gene. These res ults suggest that (i) the DDB2 gene is somewhat related to skin carcinogene sis, photoaging skin, and the removal of (6-4) photoproducts; (ii) although it is believed that cyclobutane pyrimidine dimers are the principal mutage nic lesion and (6-4) photoproducts are less likely to contribute to ultravi olet-induced mutations in mammals, Ops1 is one of the ultraviolet-induced m utagenic models induced by (6-4) photoproducts.