CYLD mutation causes multiple familial trichoepithelioma in three Chinese families

Abstract

Multiple familial trichoepithelioma (MFT) and familial cylindromatosis are two clinically distinct cancer syndromes. MFT patients developed mostly trichoepithelioma in the face while cylindromatosis patients developed cylindromas predominantly (approximately 90%) on the head and neck. However, multiple familial trichoepithelioma is occasionally associated with familial cylindromatosis while cylindromatosis patients can also develop trichoepithelioma. This has led to the speculation that the 2 types of dermatoses may be caused by dysfunction of a common pathway. Previously, a candidate MTF locus has been mapped to 9p21 while disease gene for familial cylindromatosis, the CYLD gene located on 16q21-13 has been identified. Here, we show that mutations in the CYLD gene are also the genetic basis for three different Chinese families with MFT. Sequence analysis reveal a single nucleotide deletion, c.1462delA (P.Ile488fsX9) in exon 9, a nonsense mutation, c.2128C>T (p. Gln710X) in exon 17, and a missense mutation, c.2822A>T (p. Asp941Val) in exon 21 in each of the three families respectively. This provides direct evidence that the mutations in CYLD can cause two clinically distinct cancer syndromes.

Mutations in the NF-κB signaling pathway: implications for human disease

“…Nevertheless, some CYLD patients harbor trichoepitheliomas intermingled with cylindromas (Poblete-Gutie´rrez et al, 2002). Thus, whether there was a genetic relationship between the two diseases remained unclear; however, it is now known that some MFT patients also have mutations in CYLD (Salhi et al, 2004;Zhang et al, 2004;Zheng et al, 2004) (Figure 2), suggesting that cylindromatosis and MFT are two distinct manifestations of the same genetic defect. This discovery supports the view that precursor cells of the folliculo-sebaceous hair unit are indeed the cell types that become transformed upon CYLD dysfunction.…”

NF-κB-related genetic diseases

“…In several distinct MFT families, CYLD mutations have been identified, demonstrating that both cylindromatosis and MFT share an identical genetic basis. [65][66][67] From these observations, it can be predicted that other less well-known pathologies characterized by various adnexal neoplasms may also be caused by CYLD mutations.…”

Multiple Familial Trichoepithelioma Caused by Mutations in the Cylindromatosis Tumor Suppressor Gene

“…However, in contrast to the notion of genetic identity of cylindroma and TE, defects of a tumor repressor gene on chromosome 16, CYLD, were documented to cause familial cylindromatosis (7,8). CYLD mutations were recently detected in Chinese families with MFT (9,10). Because some families with CYLD mutations were affected with both cylindromas and TEs (11,12), CYLD deficiency appears to be associated with Spiegler-Brooke syndrome (MIM 605041).…”