title: De novo mutations of the Patched gene in nevoid basal cell carcinoma syndrome help to define the clinical phenotype.
abstract: The demonstration that mutations in the Patched (PTCH) gene cause nevoid basal cell carcinoma syndrome (NBCCS) has led to the identification of the exact molecular lesion in a percentage of individuals with the syndrome. In addition, it has been possible to determine, through molecular analysis of parents and other relatives of these individuals, if the mutation is inherited or has arisen de novo. We have previously reported 28 mutations in individuals with NBCCS, and here we present an additional 4 novel mutations. We have also analyzed relatives of a number of the individuals in whom we have found mutations. In total we have identified 8 individuals who carry a de novo mutation in the PTCH gene. In 5 of these cases, clinical and radiological examination had not unequivocally ruled out a diagnosis in one of the parents. This helps to define the clinical phenotype and suggests that diagnostic criteria in this complex syndrome may require review.
authors.affiliation: Centre for Molecular and Cellular Biology, The University of Queensland, Brisbane, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Wicking
authors.forename: S
authors.initials: S
authors.lastname: Gillies
authors.forename: I
authors.initials: I
authors.lastname: Smyth
authors.forename: S
authors.initials: S
authors.lastname: Shanley
authors.forename: L
authors.initials: L
authors.lastname: Fowles
authors.forename: J
authors.initials: J
authors.lastname: Ratcliffe
authors.forename: B
authors.initials: B
authors.lastname: Wainwright
authors.forename: G
authors.initials: G
authors.lastname: Chenevix-Trench
mesh_terms: D001478:Basal Cell Nevus Syndrome / Q000235:genetics*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000032:analysis; D005091:Exons; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D018895:Microsatellite Repeats; D009154:Mutation; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D011956:Receptors, Cell Surface
chemical_list: D004273:DNA, Neoplasm; D008565:Membrane Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface