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A 10‐year follow‐up of a child with mild case of xeroderma pigmentosum complementation group D diagnosed by whole‐genome sequencing
Author(s) -
Ono Ryusuke,
Masaki Taro,
Mayca Pozo Franklin,
Nakazawa Yuka,
Swagemakers Sigrid M. A.,
Nakano Eiji,
Sakai Wataru,
Takeuchi Seiji,
Kanda Fumio,
Ogi Tomoo,
Spek Peter J.,
Sugasawa Kaoru,
Nishigori Chikako
Publication year - 2016
Publication title -
photodermatology, photoimmunology and photomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.736
H-Index - 60
eISSN - 1600-0781
pISSN - 0905-4383
DOI - 10.1111/phpp.12240
Subject(s) - xeroderma pigmentosum , ercc2 , complementation , genetics , medicine , compound heterozygosity , mutation , genome , dermatology , nucleotide excision repair , biology , dna , dna repair , gene , phenotype
Summary 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 ERCC 2 , 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/cm 2 , 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 ERCC 2 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.