MUTATIONS IN THE HUMAN HOMOLOG OF THE DROSOPHILA PATCHED GENE IN CAUCASIAN AND AFRICAN-AMERICAN NEVOID BASAL-CELL CARCINOMA SYNDROME PATIENTS

The nevoid basal cell carcinoma syndrome (NBCCS), or Gorlin syndrome, is a multisystem autosomal dominant disorder. The salient features of this syndrome include multiple basal cell carcinomas, palmar and/or pl antar pits, odontogenic keratocysts, skeletal and developmental anomal ies, and ectopic calcification. Other features include such tumors as ovarian fibromas and medulloblastomas. There is extensive interfamilia l as well as intrafamilial variability with respect to the manifestati on and severity of the phenotype. Alterations in the human homologue ( PTCH) of the Drosophila segment polarity gene patched have been identi fied in NBCCS patients as well as tumors associated with this syndrome . We report several mutations in this gene in NBCCS patients and prese nt the clinical phenotypes of the individuals in whom these mutations were identified.