Nevoid basal cell carcinoma syndrome caused by splicing mutations in the PTCH1 gene
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- 作者：Chise Kato ; Kentaro Fujii ; Yuto Arai ; Hiromi Hatsuse ; Kazuaki Nagao…
- 关键词：Nevoid basal cell carcinoma syndrome ; PTCH1 ; Splicing mutation
- 刊名：Familial Cancer
- 出版年：2017
- 出版时间：January 2017
- 年：2017
- 卷：16
- 期：1
- 页码：131-138
- 全文大小：
- 刊物类别：Medicine
- 刊物主题：Cancer Research; Human Genetics; Epidemiology; Biomedicine, general;
- 出版者：Springer Netherlands
- ISSN：1573-7292
- 卷排序：16
文摘
Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by developmental defects and tumorigenesis such as medulloblastomas and basal cell carcinomas, caused by mutations of the patched-1 (PTCH1) gene. To date, we have detected 73 mutations in PTCH1 and ten of them (14 %) were suspected splicing mutations. Eight out of the ten mutations were localized near the splice donor site. Five mutations were localized within the invariant GT-AG splice site, whereas the other five mutations occurred outside the invariant GT-AG site including the last exonic nucleotide. When the transcripts were examined, all mutations resulted in aberrant splicing, including exon skipping or the activation of cryptic splice sites. This is the first extensive report of NBCCS focusing on splice site mutations, and it highlights the importance of analyzing transcripts especially for mutations lying outside the GT-AG splicing consensus site. In addition, the splice site score calculated by Splice-Site Analyzer Tool provided by Tel Aviv University helped predict aberrant splice patterns in most of the cases.