There is abundant evidence published associating the CYLD gene with Brooke-Spiegler syndrome, since the gene-disease relationship was first proposed by Bignell et al. (2000). Multiple case level studies have been performed with BSS patients that have variants in the CYLD gene. CYLD protein is prominently expressed in the inner root sheath of hair follicles of human scalp as well as in eccrine glands. Multiple articles reported no CYLD protein expression in the tumour tissue from BSS patients. Loss of CYLD inhibits apoptosis by activating NF-kappaB. Cyld also negatively regulate cell proliferation in keratinocytes and human Cylindroma tumors display hyperactive Wnt signaling. Cyld-/- mice are highly sensitive to skin tumor development under TPA or UV-B treatment. All of these types of evidence are consistent with a definitive relationship between the CYLD gene and Brooke-Spiegler syndrome.
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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