A novel CYLD germline mutation in Brooke-Spiegler syndrome

D. Guardoli, G. Argenziano, G. Ponti, S. Nasti, I. Zalaudek, E. Moscarella, A. Lallas, S. Piana, F. Specchio, C. Martinuzzi, M. Raucci, G. Pellacani, C. Longo

Research output: Contribution to journalArticlepeer-review

Abstract

Background Brooke-Spiegler syndrome (BSS) is a rare, inherited, autosomal dominant disorder characterized by the development of multiple adnexal neoplasms including spiradenomas, cylindromas, trichoepitheliomas and major and minor salivary glands neoplasms. This syndrome encompasses a wide variability of clinical phenotypes depending on the variable number of tumours present in the given patient. Objective Somatic mutations in adjunct to CYLD germline mutations may play a central role in the development of the tumour phenotype and in the genotype-phenotype correlations. Methods Blood sample and paraffin embedded tissue biopsied from three cylindromas, one trichoepithelioma and one spiradenomas were collected after obtaining informed consent from our patient and genomic DNA was isolated. Results We found out a novel germline mutation in the CYLD gene in exon 15 that resulted in the deletion of one nucleotide. This gives rise to a premature translational termination codon at amino acid position 693 prior to four Cys-X-X-Cys pairs and one of the two catalytic domains of ubiquitin carboxy-terminal hydrolases. In only one cylindroma we detected the same germline mutation (c.2070delT/p.F690FfsX3) in addition to two somatic events (I645V and R936X). The presence of this unique mutation could be linked to the peculiar phenotype of our patient who presented an attenuated form of BSS, an autosomal dominant inheritance with low penetrance and no additional visceral tumours. Conclusions The overall phenotype of our patient may support the hypothesis that somatic mutations in adjunct to CYLD germline mutations may play a central role in the development of the tumour phenotype and in the genotype-phenotype correlations.

Original languageEnglish
Pages (from-to)457-462
Number of pages6
JournalJournal of the European Academy of Dermatology and Venereology
Volume29
Issue number3
DOIs
Publication statusPublished - Mar 1 2015

ASJC Scopus subject areas

  • Dermatology
  • Infectious Diseases
  • Medicine(all)

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