CYLD mutations underlie Brooke–Spiegler, familial cylindromatosis, and multiple familial trichoepithelioma syndromes

Abstract

Brooke-Spiegler syndrome (BSS), familial cylindromatosis (FC), and multiple familial trichoepithelioma (MFT), originally described as distinct inherited disorders, are characterized by a variety of skin appendage neoplasms. Mutations in the CYLD gene are found in individuals with these syndromes. We describe a single family with affected members exhibiting either the FC or the MFT phenotypes associated with a mutation in the CYLD gene. These findings support the notion that BSS, FC, and MFT represent phenotypic variation of a single defect. Of interest, one of the affected individuals described in this report exhibits a severe phenotype illustrating the morbidity of the disorder.

Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma

“…CYLD, located at 16q12.1, was first identified as the relevant tumor suppressor gene in cylindroma tumors, a form of hereditary skin tumor. 48 Mutation of CYLD has been detected in cylindroma cases, 49 and mutations have been noted in myeloma. 50 CYLD is known to function as a negative regulator of the NF-B pathway, [34][35][36] and recent studies suggest that CYLD acts via the noncanonical NF-B pathway.…”

Trichoepithelioma of thigh. Third reported case

“…An abnormality in this gene may result in one of three syndromes Brooke-Spiegler syndrome, familial cylindromatosis, and multiple familial trichoepithelioma. 1 We can find about thirteen reported cases in literature, and there is two reported trichoepithelioma of the thigh. Our case is the 3rd cases reported trichoepithelioma of thigh to our knowledge.…”

CYLD Cutaneous Syndrome: Familial Cylindromatosis, Brooke-Spiegler Syndrome and Multiple Familial Trichoepitherioma

“…The germline mutations were then detected in individuals with BSS (HU et al, 2003;Poblete Gutiérrez et al, 2002) and MFT (Salhi et al, 2004;Zhang et al, 2004;Zheng et al, 2004). Affected family members with the same germline mutation in CYLD showed FC, BSS or MFT phenotypes, indicating the absence of genotype-phenotype relationship (Fenske et al, 2000;Rajan et al, 2009;Young et al, 2006). The phenotypic diversity from mild type to severe turban tumor is present in the affected family members with CYLD cutaneous syndrome (Biggs et al, 1995;Oiso et al, 2004;Rajan et al, 2009;Young et al, 2006).…”

“…Affected family members with the same germline mutation in CYLD showed FC, BSS or MFT phenotypes, indicating the absence of genotype-phenotype relationship (Fenske et al, 2000;Rajan et al, 2009;Young et al, 2006). The phenotypic diversity from mild type to severe turban tumor is present in the affected family members with CYLD cutaneous syndrome (Biggs et al, 1995;Oiso et al, 2004;Rajan et al, 2009;Young et al, 2006). Bowen et al suggested that FC, BSS, and MTF represent phenotypic variation of a single entity (Bowen et al, 2005).…”