A novel missense mutation in CYLD in a family with Brooke-Spiegler syndrome

Journal of Drugs in Dermatology, Jan-Feb, 2004 by G. Hu, M. Onder, M. Gill, B. Aksakal, M. Oztas, M.A. Gurer, J.T. Celebi

The authors present a missense mutation in CYLD in a family with Brooke-Spiegler syndrome (BSS). BSS is an inherited disease characterized by neoplasms of the skin appendages such as cylindroma, trichoepithelioma, and spiradenoma. BSS has been mapped to 16q12-13, and mutations in the CYLD gene. Multiple familial trichoepithelioma (MFT) has been described as a distinct disorder characterized by the familial occurrence of trichoepitheliomas; no candidate gene has been identified, yet it has been mapped to 9p21. The authors describe a four-generation family with BSS presenting predominantly with trichoepitheliomas (resembling MFT phenotype). The authors identified a novel missense mutation in the CYLD gene, designated E474G, in the affected individuals of this family. The authors demonstrate phenotypically heterogeneity within BSS and extend the body of evidence that mutations in CYLD are implicated in this disease.

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The authors expand on our knowledge of the genetics of the CYLD gene. Previous to this study, the CYLD gene was unique to BSS. They state that only one inactivated copy is needed to cause neoplasms, this suggests a possible tumor suppressor activity of this gene. Therefore, the phenotypic variability depends on how many gene copies are inactivated. Furthermore, BSS has been postulated to be more of a spectrum disease, confirming the authors' suspicions. Future directions would include additional familial studies with MFT and BSS to further evaluate the similarities and variabilities of these disorders.

J Invest Dermatol 2003 Oct; 121(4):732-4.