Nevoid basal cell carcinoma syndrome caused by splicing mutations in the PTCH1 gene

AbstractNevoid 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 thepatched-1 (PTCH1) gene. To date, we have detected 73 mutations inPTCH1 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. Whe n 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 mut ations 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.
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research