Possible new complementation group of xeroderma pigmentosum

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Xeroderma pigmentosum (XP) is an autosomal recessive photosensitive disease with abnormal pigmentation and an extremely high incidence of skin cancers. Cells from patients with XP are hypersensitive to killing by ultraviolet (UV), which is associated with impaired ability to repair UV-induced DNA damages. There are genetically different seven nucleotide excision repair (NER) deficient groups (A～G) and a NER proficient form (XP variant). We have been receiving more than 348clinical samples for the diagnosis of XP for these five years and 108 patients were newly diagnosed as having XP in our laboratory. Among them, we found 8 unusual Japanese XP cases. Those patients (17～55 y.o.) are not related and have mild clinical features with a few skin cancers in areas exposed to sunlight and so far any evidence for neurological abnormalities was not detected. Fibroblasts derived from those patients were hypersensitive to UV irradiation compared to cells from normal subjects and less sensitive to UV than XP-A XP-C and XP-D cells, while the levels of post-UV unscheduled DNA synthesis (UDS) in those patients were less than 30% of normal, respectively. Complementation test by cell fusion technique and a plasmid host cell reactivation assay revealed that those patients did not belong to XP group A, B, C, D, F and G. DNA repair studies and gene analysis indicated that those patients were not in XP group E and XP variant. Cell fusion analysis using those cell strains implied that there were at least two more new XP complementation groups. cDNA and miRNA microarray analyses showed the decreased expression of ATM, CLSPN and FANCD. Continuing molecular and biochemical analyses using the cells from those patients should give a new insight in NER pathway.