A novel missense mutation of CYLD gene in a Chinese family with multiple familial trichoepithelioma
Multiple familial trichoepithelioma (MFT, OMIM 601606) is an autosomal dominantly inherited disease characterized by numerous, skin-colored papules with pilar differentiation. The skin tumors usually occur on the face, especially around the nasolabial folds, and more commonly found in females between the first and second decade of the life. Mutations in the CYLD gene on chromosome 16q12-q13 have been identified as the molecular basis of MFT , which is also responsible for familial cylindromatosia (FC, cylindromas only) , and Brooke-Spiegler syndrome (BSS, a combination of cylindromas, trichoepitheliomas and spiradenomas) . CYLD gene functions as a tumor suppressor, while CYLD protein is a deubiquitinating enzyme, which negatively regulates activation of the transcription factor NF-κB by removing lysine-63-linked ubiquitin chains from TRAF2 (tumor necrosis factor receptor-associated factor 2), TRAF6 and NEMO (NF-κB essential modulator, also known as IκB kinase γ, Ikkγ) ,  and . Loss of the deubiquitinating activity of CYLD correlates with tumorigenesis. In this study, we performed mutation analysis of the CYLD gene in one three-generation Chinese MFT family and summarized clinical features and CYLD gene mutations of the MFT families previously reported. The family (Fig. 1a), which included four affected individuals, was identified through the proband from Fujian province of China. The proband was a 29-year-old woman. Some small asymptomatic papules were firstly noticed on the back of nose when she was 16 years old, and the papules enlarged in size and increased in number gradually. Physical examination indicated numerous, skin-colored, dome-shaped papules and nodules of varying sizes on her face, mainly around the root and ala of her nose and on her forehead (Fig. 1b). Lesional skin biopsy revealed numerous horn cells, islands of basaloid cells with palisading periphery (Fig. 1c). The family history revealed that the four affected individuals belonging to three consecutive generations had similar clinical manifestations (Table 1a). All the patients had papules or nodules around the noses. The average onset age of this family was about 15 years old varying from 10 to 16. There was no consanguinity in the family.