Keratocystic odontogenic tumors (KCOTs) are locally aggressive jaw lesions that may be related to PTCH1 mutations in isolation or in association with nevoid basal cell carcinoma syndrome.
In addition, a total of 204 PTCH1 mutations (187 mutations from 210 cases with NBCCS-associated and 17 mutations from 57 cases with sporadic KCOTs) were compiled from 78 published papers.
Multiple tumor types including leiomyoma and Wilms tumor in a patient with Gorlin syndrome due to 9q22.3 microdeletion encompassing the PTCH1 and FANC-C loci.
The proband and his child were identified as gene carriers of the novel K729MPTCH1 missense mutation; other first- and second-degree relatives presented clinical features of NBCCS.
This is the first reported case of NBCCS due to a tandem multiexon duplication of PTCH1 representing a novel mechanism leading to the NBCCS phenotype, and highlights the importance of copy number analysis as an adjunct to exon sequencing in identifying infrequent mutational events in PTCH1.
Basal cell nevus syndrome (BCNS), also known as Gorlin syndrome (OMIM #109400) is a well-described rare autosomal dominant condition due to haploinsufficiency of PTCH1.
These results clearly demonstrate that a selective haploinsufficiency of longer isoforms of the PTCH1 protein, PTCHL and PTCHM, but not PTCHS is sufficient to cause NBCCS.
Patched 1 gene mutation has also been identified as the underlying mechanism in most cases of Gorlin syndrome (also known as basal cell nevus syndrome or nevoid basal cell carcinoma syndrome).
Both inherited and acquired mutations of patched 1 (PTCH1), a tumor-suppressor gene controlling the activity of Smoothened (SMO), are the primary cause of the constitutive activation of the Hedgehog (HH) pathway, leading to the emergence of BCCs in NBCCS.
Most associate with Gorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS, MIM #109400) due to haploinsufficiency of the PTCH1 gene (MIM *601309).
The possibility of Gorlin syndrome in this family was excluded by both the absence of any clinical and radiological features and the lack of mutation in PTCH1.
The human homologue of the Drosophila segment polarity gene PTCH1, a tumor suppressor gene within the Sonic Hedgehog pathway has been implicated as the mutation responsible for nevoid basal cell carcinoma syndrome (NBCCS) as well as many other sporadic neoplasms.