Tanioka Miki, Takahashi Katsu, Kawabata Tomohiro, Kosugi Shinji, Murakami Kenichiro, Miyachi Yoshiki, Nishigori Chikako, Iizuka Tadahiko
Department of Dermatology, Graduate School of Medicine, Kobe University, 7 Kusunoki-cho, Shogoin, Chuo-ku, Kobe, 651-0017, Japan.
Arch Dermatol Res. 2005 Jan;296(7):303-8. doi: 10.1007/s00403-004-0520-1. Epub 2004 Nov 23.
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.
我们在8名无亲缘关系的日本痣样基底细胞癌综合征（NBCCS）患者中鉴定出7种新的PTCH基因种系突变。为确保基因诊断，通过聚合酶链反应（PCR）从基因组DNA中扩增PTCH基因的所有23个编码外显子并进行测序。在所有8例NBCCS患者中均发现了突变。本研究中检测到的突变包括1个插入/缺失突变、1个1碱基插入、2个1碱基缺失、1个无义突变和2个错义突变。这些突变此前均未见报道。5个突变导致过早出现终止密码子，预计会产生截短的蛋白质。在这2个错义突变中，强碱性残基精氨酸在PTCH假定跨膜结构域的高度保守区域被丝氨酸或甘氨酸取代，因此这些突变可能会影响PTCH蛋白的构象和功能。在日本NBCCS患者中未发现表型-基因型关系，这与之前对非裔美国人和白种人NBCCS患者的研究结果一致。
