Germline mutations of the PTCH gene in Japanese patients with nevoid basal cell carcinoma syndrome
Germline mutations of the PTCH gene in Japanese patients with nevoid basal cell carcinoma syndrome
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DOI：
10.1007/s00403-004-0520-1
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发表时间：
2005-01-01
影响因子：
3
通讯作者：
Iizuka, T
中科院分区：
文献类型：
--
作者：
Tanioka, M;Takahashi, K;Iizuka, T
我们在8例无亲缘关系的日本基底细胞癌综合征（NBCCS）患者中发现了7个新的PTCH基因种系突变。为了确保基因诊断，采用聚合酶链反应（PCR）从基因组DNA中扩增出PTCH基因的全部23个编码外显子并测序。在所有8例NBCCS患者中均发现突变。本研究检测到的突变包括1个插入/缺失突变、1个1-bp插入、2个1-bp缺失、1个无义突变和2个错义突变。这些突变以前都没有报道过。五种突变导致过早终止密码子，预计会导致截断的蛋白质。在这两种错义突变中，强碱性残基精氨酸被推测为PTCH跨膜结构域的高度保守成分的丝氨酸或甘氨酸取代，因此这些突变可能影响PTCH蛋白的构象和功能。在日本的NBCCS患者中未发现表型-基因型关系，这与之前关于非裔美国人和高加索人NBCCS患者的研究结果一致。
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.