Abstract
We identified seven novel germline mutations of the PTCH gene in eight unrelated Japanese patients with nevoid basal cell carcinoma syndrome (NBCCS). In order to ensure genetic diagnosis, all 23 coding exons of the PTCH gene were amplified from genomic DNA by polymerase chain reaction (PCR) and sequenced. Mutations were found in all eight patients with NBCCS. The mutations detected in this study include one insertion/deletion mutation, one 1-bp insertion, two 1-bp deletions, one nonsense mutation and two missense mutations. None of the mutations have been previously reported. Five mutations caused premature stop codons that are predicted to result in a truncated protein. In the two missense mutations, the strong basic residue arginine was substituted by serine or glycine in highly conserved components of the putative transmembrane domain of PTCH, and these mutations may therefore affect the conformation and function of the PTCH protein. No phenotype-genotype relationships were found in the Japanese NBCCS patients, consistent with results of previous studies on NBCCS in African-American and Caucasian patients.
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Acknowledgements
We would like to thank all of the patients and families who contributed to this study. We are grateful to Dr. K. Fujimura and Dr. I. Yamamura (Kyoto University) for providing blood samples from patients with NBCCS. We are deeply indebted to Dr. I. Tojo, Dr. I. Miyamoto and Dr. A. Segawa (Kyoto University) for their technical assistance. This work was supported by grants from the Ministry of Education, Science, Sports and Culture of Japan.
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M. Tanioka and K. Takahashi contributed equally to this work.
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Tanioka, M., Takahashi, K., Kawabata, T. et al. Germline mutations of the PTCH gene in Japanese patients with nevoid basal cell carcinoma syndrome. Arch Dermatol Res 296, 303–308 (2005). https://doi.org/10.1007/s00403-004-0520-1
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DOI: https://doi.org/10.1007/s00403-004-0520-1