Background: Most patients with xeroderma pigmentosum complementation group D (XP-D) from Western countries suffer from neurological symptoms, whereas Japanese patients display only skin manifestations without neurological symptoms. We have previously suggested that these differences in clinical manifestations in XP-D patients are attributed partly to a predominant mutation in ERCC2, and the allele frequency of S541R is highest in Japan. Methods: We diagnosed a child with mild case of XP-D by the evaluation of DNA repair activity and whole-genome sequencing, and followed her ten years. Results: Skin cancer, mental retardation, and neurological symptoms were not observed. Her minimal erythema dose was 41 mJ/cm2, which was slightly lower than that of healthy Japanese volunteers. The patient's cells showed sixfold hypersensitivity to UV in comparison with normal cells. Post-UV unscheduled DNA synthesis was 20.4%, and post-UV recovery of RNA synthesis was 58% of non-irradiated samples, which was lower than that of normal fibroblasts. Genome sequence analysis indicated that the patient harbored a compound heterozygous mutation of c.1621A>C and c.591_594del, resulting in p.S541R and p.Y197* in ERCC2: then, patient was diagnosed with XP-D. Y197* has not been described before. Conclusion: Her mild skin manifestations might be attributed to the mutational site on her genome and daily strict sun protection. c.1621A>C might be a founder mutation of ERCC2 among Japanese XP-D patients, as it was identified most frequently in Japanese XP-D patients and it has not been found elsewhere outside Japan.

Additional Metadata
Keywords nucleotide excision repair, recovery of RNA synthesis, unscheduled DNA synthesis, whole genome sequence, xeroderma pingmentosum
Persistent URL dx.doi.org/10.1111/phpp.12240, hdl.handle.net/1765/96993
Journal Photodermatology Photoimmunology and Photomedicine
Citation
Ono, R. (Ryusuke), Masaki, T. (Taro), Mayca Pozo, F. (Franklin), Nakazawa, Y. (Yuka), Swagemakers, S.M.A, Nakano, E. (Eiji), … Nishigori, C. (2016). A 10-year follow-up of a child with mild case of xeroderma pigmentosum complementation group D diagnosed by whole-genome sequencing. Photodermatology Photoimmunology and Photomedicine, 32(4), 174–180. doi:10.1111/phpp.12240