title: Xeroderma pigmentosum complementation group G patient with a novel homozygous missense mutation and no neurological abnormalities.
abstract: We describe an unusual xeroderma pigmentosum (XP) patient with a mutation in XP complementation group G, representing only the third reported Japanese XP-G patient. A 40-year-old men (XP3HM), born from consanguineous parents experienced sun sensitivity and pigmentary changes of sun-exposed skin since childhood. He developed a squamous cell carcinoma on his lower lip at the age of 40. He has neither neurological abnormalities nor Cockayne syndrome. The primary fibroblasts of the patient were hypersensitive to killing by UV (D(0) = 0.6 J/m(2)) and the post-UV unscheduled DNA synthesis was 8% of normal. Host cell reactivation complementation analysis implicated XP complementation group G. We identified a novel homozygous mutation (c.194T>C) in a conserved portion of the XPG(ERCC5) gene, resulting in a predicted amino acid change; p.L65P. We confirmed that this genetic change reduced DNA repair thus linking this mutation to increased skin cancer.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Moriwaki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takigawa
authors.forename: Naoya
authors.initials: N
authors.lastname: Igarashi
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Nagai
authors.forename: Hiroo
authors.initials: H
authors.lastname: Amano
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishikawa
authors.forename: Sikandar G
authors.initials: SG
authors.lastname: Khan
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Kraemer
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008048:Lip Neoplasms / Q000235:genetics; D008297:Male; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014983:Xeroderma Pigmentosum / Q000145:classification / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5