The novel PTCH mutation and clinical manifestations within Gorlin syndrome family links PTCH haploinsufficiency and aberrant activation of the Wnt pathway. We report a family case with Gorlin syndrome, characterized by the usual phenotype features such as widespread basocellular tumors and craniofacial and bone malformations, but also including a less common appearance of craniopharyngioma. These clinical manifestations might be associated with a novel constitutional mutation of the PTCH gene, 1047insAGAA, which we found in exon 7. It changes the normal amino acid sequence leading to termination of the PTCH protein at exon 9. The analyzed tumors of the family show extensive loss of heterozygosity in the PTCH region, both basocellular and in particular craniopharyngioma, and in the latter a high expression of β-catenin was detected. Our findings suggest involvement of the SHH/PTCH/SMO pathway in pathogenesis of the analyzed disorders, including its possible contribution to aberrant activation of the Wnt pathway in craniopharyngioma.

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