CYLD mutations in familial skin appendage tumours

Saggar, S. and Chernoff, K. A. and Lodha, S. and Horev, L. and Kohl, S. and Honjo, R. S. and Brandt, H. R. C. and Hartmann, K. and Celebi, J. T.. (2008) CYLD mutations in familial skin appendage tumours. Journal of medical genetics, 45 (5). pp. 298-302.

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Official URL: https://edoc.unibas.ch/70830/

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Germ-line mutations in CYLD are found in patients with familial skin appendage tumours. The protein product functions as a deubiquitinase enzyme, which negatively regulates NF-kappaB and c-Jun N-terminal kinase signalling. Brooke-Spiegler syndrome (BSS) is characterised by cylindromas, trichoepitheliomas and spiradenomas, whereas in familial cylindromatosis (FC) patients present with cylindromas and in multiple familial trichoepitheliomas (MFT) with trichoepitheliomas as the only skin tumour type. Although described as distinct entities, recent studies suggest that they are within the spectrum of a single entity.; To investigate the mutation spectrum of CYLD and possible genotype-phenotype correlations.; 25 families including 13 BSS, 3 FC, and 9 MFT families were examined and evaluated for mutations in the CYLD gene.; In total, 18 mutations in CYLD, including 6 novel mutations, were identified in 25 probands (72%). The mutation frequencies among distinct phenotypes were 85% for BSS, 100% for FC, and 44% for MFT. The majority of the mutations were insertions, deletions or nonsense mutations leading to formation of truncated proteins. All mutations were located between exons 9 to 20, encoding the NEMO binding site and the catalytic domain. Genotype-phenotype analysis failed to reveal a correlation between the types of mutations and their location within the gene and the patients' phenotypes and disease severity.; This study provides further evidence on the role of CYLD in the pathogenesis of skin appendage tumours characterised by cylindromas, trichoepitheliomas and/or spiradenomas, but the molecular mechanisms of CYLD in skin tumorigenesis and the reasons for phenotypic variability remain to be explored.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Allergy and Immunity (Hartmann)
UniBasel Contributors:Hartmann, Karin
Item Type:Article, refereed
Article Subtype:Further Journal Contribution
Publisher:British Medical Association
Note:Publication type according to Uni Basel Research Database: Journal item
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Last Modified:10 Nov 2020 14:31
Deposited On:10 Nov 2020 14:31

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