1. ¹Department of Dermatology, Graduate School of Medicine, Kobe University, Kobe, Japan
2. ²Department of Dermatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
3. ³Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan
4. ⁴DNA Repair Section, Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA
5. ⁵Photon Medical Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan

Correspondence: Dr Chikako Nishigori, Division of Dermatology, Graduate School of Medicine, Kobe University, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. E-mail: chikako@med.kobe-u.ac.jp

⁶These authors contributed equally to this work.

Received 14 September 2006; Revised 26 November 2006; Accepted 20 December 2006; Published online 8 March 2007.

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.