title: Molecular analysis of DNA polymerase eta gene in Japanese patients diagnosed as xeroderma pigmentosum variant type.
abstract: POLH mutations were identified in 16 Japanese patients, who were diagnosed, both clinically and at a cellular level, as being of the xeroderma pigmentosum variant type (XPV). While all the patients developed skin cancer with an average onset of the cancer at 45 years, in non-XP Japanese the onset was at over 70 years. All the cell strains from the patients were normal or slightly hypersensitive to UV and most of these showed enhanced UV sensitivity when the post-UV colony formation was performed in the presence of caffeine. Immunoprecipitation analysis with two kinds of anti-POLH protein antibodies revealed that cells from 13 patients did not show the 83 kDa POLH band and that cells from one patient had a faint 83 kDa band. All of these 14 cell strains, without a POLH band or with a weak POLH band, had mutations in the POLH gene. The IP analysis of the POLH protein revealed a very useful method for screening the patients suspected of XPV. Seven mutations in the POLH gene including three novel mutations were identified. Among the mutations detected, 11 alleles out of 28 (39%) were G490T mutations.
authors.affiliation: Department of Dermatology, Graduate School of Medicine, Kobe University, Kobe, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Tanioka
authors.forename: Taro
authors.initials: T
authors.lastname: Masaki
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Ono
authors.forename: Tohru
authors.initials: T
authors.lastname: Nagano
authors.forename: Eriko
authors.initials: E
authors.lastname: Otoshi-Honda
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takigawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Inui
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Miyachi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Moriwaki
authors.forename: Chikako
authors.initials: C
authors.lastname: Nishigori
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D001706:Biopsy; D016022:Case-Control Studies; D002478:Cells, Cultured; D004273:DNA, Neoplasm / Q000378:metabolism / Q000528:radiation effects; D004259:DNA-Directed DNA Polymerase / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000201:enzymology / Q000473:pathology; D012878:Skin Neoplasms / Q000235:genetics*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics*; D000099270:Y-Family DNA Polymerases
chemical_list: D004273:DNA, Neoplasm; D004259:DNA-Directed DNA Polymerase; D012333:RNA, Messenger; C112338:Rad30 protein; D000099270:Y-Family DNA Polymerases