title: A 10-year follow-up of a child with mild case of xeroderma pigmentosum complementation group D diagnosed by whole-genome sequencing.
abstract: 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/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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Ono
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Masaki
authors.affiliation: Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, Kobe, Japan.
authors.forename: Franklin
authors.initials: F
authors.lastname: Mayca Pozo
authors.affiliation: Nagasaki University Research Centre for Genomic Instability and Carcinogenesis, Nagasaki University, Nagasaki, Japan.|Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nakazawa
authors.affiliation: Department of Bioinformatics, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Sigrid M A
authors.initials: SM
authors.lastname: Swagemakers
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakano
authors.affiliation: Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, Kobe, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Sakai
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Takeuchi
authors.affiliation: Division of Neurology, Kobe University Graduate School of Medicine, Kobe, Japan.|Integrated Clinical Education Center, Kobe University Hospital, Kobe, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Kanda
authors.affiliation: Nagasaki University Research Centre for Genomic Instability and Carcinogenesis, Nagasaki University, Nagasaki, Japan.|Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Ogi
authors.affiliation: Department of Bioinformatics, Erasmus University Medical Centre, Rotterdam, The Netherlands.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: van der Spek
authors.affiliation: Biosignal Research Center, Organization of Advanced Science and Technology, Kobe University, Kobe, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Sugasawa
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Nishigori
mesh_terms: D002648:Child; D005260:Female; D005500:Follow-Up Studies; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007564:Japan; D009154:Mutation; D014983:Xeroderma Pigmentosum / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
chemical_list: D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human
keywords: nucleotide excision repair; recovery of RNA synthesis; unscheduled DNA synthesis; whole genome sequence; xeroderma pingmentosum