title: Brooke-Spiegler syndrome: report of two cases not associated with a mutation in the CYLD and PTCH tumor-suppressor genes.
abstract: Brooke-Spiegler syndrome represents an autosomal dominant disease characterized by the occurrence of multiple cylindromas, trichoepitheliomas and (sporadically) spiroadenomas. Patients with Brooke-Spiegler syndrome are also at risk of developing tumors of the major and minor salivary glands. Patients with Brooke-Spiegler syndrome have various mutations in the CYLD gene, a tumor-suppressor gene located on chromosome 16q. To date, 68 unique CYLD mutations have been identified. We describe two families with Brooke-Spiegler syndrome, one with familial cylindromatosis and one with multiple familial trichoepithelioma, which showed wide inter-family phenotypic variability. Analysis of germline mutations of the CYLD and PTCH genes was performed using peripheral blood. In addition, formalin-fixed paraffin-embedded tumor samples were analyzed for PTCH somatic mutations and cylindroma cell cultures were obtained directly from patients for further growth and analysis. Clinically, the major features of Brooke-Spiegler syndrome include the presence of heterogeneous skin tumors and wide inter- and intra-familial phenotypic variability. Histopathologically, both cylindromas and trichoepitheliomas were found in affected individuals. Mutations or loss of heterozygosity was not found in CYLD and PTCH genes. In CYLD and PTCH mutation-negative patients, other genes may be affected and further studies are needed to clarify whether these patients may be affected by de novo germline mutations.
authors.affiliation: Division of Dermatology, Department of Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy. ponti.giovanni@unimore.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ponti
authors.forename: Sabina
authors.initials: S
authors.lastname: Nasti
authors.forename: Lorena
authors.initials: L
authors.lastname: Losi
authors.forename: Lorenza
authors.initials: L
authors.lastname: Pastorino
authors.forename: Annamaria
authors.initials: A
authors.lastname: Pollio
authors.forename: Luisa
authors.initials: L
authors.lastname: Benassi
authors.forename: Stefania
authors.initials: S
authors.lastname: Giudice
authors.forename: Giorgia
authors.initials: G
authors.lastname: Bertazzoni
authors.forename: Eugenia
authors.initials: E
authors.lastname: Veratti
authors.forename: Paola
authors.initials: P
authors.lastname: Azzoni
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bianchi Scarrà
authors.forename: Stefania
authors.initials: S
authors.lastname: Seidenari
mesh_terms: D000074749:Deubiquitinating Enzyme CYLD; D005190:Family; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics* / Q000473:pathology; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics* / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; C409984:CYLD protein, human; D000074749:Deubiquitinating Enzyme CYLD