The cause of the syndrome is a mutation in the PTCH1 tumor-suppressor gene at chromosome 9q22.3, which inhibits the hedgehog signaling pathway.
Leffell was a member of the international team that discovered PTC1, a tumor suppressor gene that plays a critical role in the development of hereditary and sporadic basal cell cancer.
The protein encoded by this gene localizes to the cytoplasm and activates patched Drosophila homolog (PTCH) gene expression.
The protein encoded by this gene localizes in the cytoplasm and activates patched Drosophila homolog (PTCH1) gene expression.
Among his laboratory's many subsequent discoveries, he is recognized for the cloning of the patched gene family and demonstration that a human homolog PTCH1 is a key tumor suppressor gene for the Hedgehog signaling pathway as well as the causative gene for the nevoid basal cell carcinoma syndrome, or Gorlin syndrome.
Recurrent mutations in the genes CTNNB1, PTCH1, MLL2, SMARCA4, DDX3X, CTDNEP1, KDM6A and TBR1 were identified in individuals with medulloblastoma.
They form a classic group for the study of medullablastoma and other cancers and include mice lines that are KO for p53, Ptch1, and Ink4c.
Recent work in molecular genetics has shown NBCCS to be caused by mutations in the PTCH (Patched) gene found on chromosome arm 9q.
Stimulation of the patched receptor by the sonic hedgehog ligand leads to translocation of SMO to the primary cilium.