Brooke-Spiegler syndrome (BSS) is an inherited autosomal dominant disease characterized by the development of multiple adnexal cutaneous neoplasms most commonly spiradenoma, cylindroma, spiradenocylindroma, and trichoepithelioma. Multiple familial trichoepithelioma (MFT) is a phenotypic variant of the disease characterized by the development of numerous trichoepitheliomas (cribriform trichoblastoma) only. Malignant tumors arise in association with preexisting benign cutaneous neoplasms in about 5-10% of the patients . Apart from the skin, major and minor salivary glands have been rarely involved in BSS patients. Extremely rare is the occurrence of breast tumors (cylindroma). The gene implicated in the pathogenesis of the disease is the CYLD gene, a tumor suppressor gene located on chromosome 16q12-q13. Germline CYLD mutations are detected in about 80-85% of patients with the classical BSS phenotype and in about 40-50% of the individuals with the MFT phenotype using a PCR based approach with analysis of exonic sequences and exon-intron junctions of the CYLD gene. There appears to be no genotype-phenotype correlations with respect to the severity of the disease, the possibility of malignant transformation, and development of extracutaneous lesions.

• Klíčová slova
• Brooke-Spiegler syndrome, CYLD gene, Cylindroma, Spiradenoma, Trichoepithelioma,
• MeSH
• dědičné nádorové syndromy * genetika   patologie   MeSH
• deubikvitinizační enzym CYLD MeSH
• fenotyp MeSH
• genotyp MeSH
• lidé MeSH
• nádorové supresorové proteiny genetika   MeSH
• nádory kůže * genetika   patologie   MeSH
• zárodečné mutace MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• CYLD protein, human MeSH Prohlížeč
• deubikvitinizační enzym CYLD MeSH
• nádorové supresorové proteiny MeSH

BACKGROUND: Multiple familial trichoepithelioma type 1 (MFT1; MIM 601606), a rare monogenic skin disease with autosomal dominant inheritance, is characterized by the development of multiple skin-colored papules on the central area of the face, frequently occurring in the nasolabial area. The disease is associated with various mutations in the cylindromatosis (CYLD; MIM 605018) gene that are also responsible for familial cylindromatosis (FC) and Brooke-Spiegler syndrome (BSS). METHODS: Recently we have identified a Spanish MFT1 pedigree with two affected family members (father and daughter). Direct sequencing of the CYLD gene revealed a worldwide recurrent heterozygous nonsense mutation (c.2272C/T, p.R758X) in the patients. RESULTS: This mutation has already been detected in patients with all three clinical variants - BSS, FC and MFT1 - of the CYLD-mutation spectrum. Haplotype analysis was performed for the Spanish patients with MFT1, Dutch patients with FC and an Austrian patient with BSS, all of whom carry the same heterozygous nonsense p.R758X CYLD mutation. CONCLUSIONS: Our results indicate that this position is a mutational hotspot on the gene and that patients carrying the mutation exhibit high phenotypic diversity.

• MeSH
• dědičné nádorové syndromy diagnóza   genetika   MeSH
• deubikvitinizační enzym CYLD MeSH
• fenotyp MeSH
• haplotypy MeSH
• heterozygot MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové supresorové proteiny genetika   MeSH
• nádory kůže diagnóza   genetika   MeSH
• nesmyslný kodon * MeSH
• rodokmen MeSH
• sekvenční analýza DNA MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Nizozemsko MeSH
• Rakousko MeSH
• Španělsko MeSH
• Názvy látek
• CYLD protein, human MeSH Prohlížeč
• deubikvitinizační enzym CYLD MeSH
• nádorové supresorové proteiny MeSH
• nesmyslný kodon * MeSH