A case of Brooke-Spiegler syndrome with a new mutation in the <i>CYLD</i> gene

Abstract

Conflicts of interest: None declared. Familial cylindromatosis (syn.: Brooke–Spiegler syndrome; MIM 132700), a rare autosomal dominant inherited disorder, is characterized by the development of multiple adnexal skin tumours (especially cylindromas, trichoepitheliomas and spiradenomas) arising from the apocrine and eccrine glands. They most commonly occur between the first and second decade of life on the face, scalp or, less frequently, neck and trunk. Malignant transformation is rare, but should be considered in clinically altered lesions. Mutations in the CYLD gene (MIM *605018; previously known as CYLD1) on chromosome 16q12–13 were identified to be responsible for the disease.1, 2 The CYLD gene spans over 56 kb of genomic DNA and contains 20 exons. Exons 4–20 encode for a product of 956 amino acids, which is expressed in different tissues. The CYLD protein, a member of the family of deubiquitinating enzymes (DUBs), contains a C‐terminal ubiquitin‐specific protease domain and plays an indispensible role in the NF‐κB signalling pathway. Post‐translational modification of proteins by attachment of ubiquitin is a common event to target them for proteasomal degradation or other cellular processes. DUBs reverse these effects by removing ubiquitin from substrate proteins. NEMO, the regulatory subunit of the inhibitor κB kinase complex, and the tumour necrosis factor receptor‐associated factor 2 (TRAF‐2), are the main targets of CYLD, which negatively regulates NF‐κB (Fig. 1). Inhibition of CYLD enhances activation of the transcription factor NF‐κB and leads to increased resistance to apoptosis and advanced carcinogenesis.3–5