The effects of splice site mutations in patients with naevoid basal cell carcinoma syndrome

We have previously identified the human homologue of the Drosophila patched gene and have described, in this gene, mutations that give rise to naevoid basal cell carcinoma syndrome (NBCCS). Here, we have analysed the effects of three splice site mutations within human PATCHED (PTCH) by the reverse transcription/polymerase chain reaction method in cultured patient lymphocyte cell lines. Two alterations, a point mutation in intron 7 and an insertion in intron 10, lead to premature truncation of the PATCHED protein. Another point mutation in intron 17 results in the skipping of exon 18 and the subsequent in-frame deletion of 46 amino acids. Additionally, in all lymphocyte and keratinocyte cell lines examined, exon 10 of PTCH is alternatively spliced leading to an in-frame deletion of 52 amino acids.