| Background Multiple familial trichoepithelioma(MFT) is a rare autosomal dominantly inherited disease characterized by benign multiple skin appendage tumors that differentiate to hair follicles. The onset age of the disease is usually during early childhood and adolescence. It is more commonly found in females. The lesions are characterized by appearance of grouped, dome-shaped, firm skin-colored nodules and papules on the face, especially, around the nasolabial folds. The patients usually had no subjective symptom or occasionally felt pruritic. The papules can increase in number and size throughout adult life. Most cases of MFT had been reported in America and Europe, although it occurs in every ethnic origin all over the world. The gene for MFT was mapped to chromosome 16q12-16q13 by microsatellite markers and linkage analysis by Zhang et al. Besides, a four-base-deletion mutation c.2355-2358delCAGA was found in exon 18 of CYLD gene, firstly confirmed in the world that the pathogenic gene of MFT is CYLD gene, which is also responsible for familial cylindromatosis and Brooke-Spiegler syndrome. CYLD gene is a tumor suppressor gene, and CYLD is a deubiquitinating enzyme, that negatively regulates activation of the transcription factor NF-κB by specific tumour necrosis factor receptors (TNFRs). Mutations of CYLD gene lead to dysfunction of CYLD protein, resulting in excessive activation of NF-κB and tumorigenesis. To date, there have been 33 germline mutations described in the CYLD gene in cases of MFT, FC and BSS, but only 8 mutations led to the clinical features of MFT, no clear correlation between phenotype and genotypes has been established.Objectives (1)To report a Chinese pedigree with MFT and detect mutations of CYLD gene in this family members. (2)To delineate the clinical and genetic features of MFT cases by literature review. Methods (1)We investigated a Chinese family with MFT, collected clinical datas and blood samples from them. (2)Genomic DNA was extracted from peripheral blood. The whole coding region and boundary sequence of CYLD were amplified by polymerase chain reaction and products analyzed by direct sequencing. 100 unrelated population- matched were made. (3)All reported papers about MFT with CYLD mutations were reviewed and the genetic and clinical features were summarized.Results (1)Four individuals belonging to three consecutive generations were similarly affected in this MFT family.(2)A novel missense mutation c.2711C>T(p.P904L) was detected in CYLD gene of all affected people. This mutation was not found in the healthy members of the family and 100 unrelated control individuals. (3)We summarized eight reported MFT families with CYLD gene mutations and the family in our research. Most probands (88.99%) had lesions around noses and all the CYLD mutations located on exon 10-20.Conclusions (1)The novel mutation (c.2711C>T) in the CYLD gene seems to be the pathogenic mutation in all affected individuals in this family.(2)There was no clear correlation between genotypes and phenotypes from the literature review. |
