Study On The Mutations Of CYLD Gene In Multiple Familial Trichoepithelioma

Background: Trichoepithelioma( TE) is a rare skin adnexal neoplasm with follicular differentiation. TE is divided into multiple trichoepithelioma, solitary trichoepithelioma and desmoplastic trichoepithelioma. Multiple trichoepithelioma is related to genetic, most of them have a family history and manifest autosomal dominant disorder. Multiple hemispherical firm papules which symmetrical scatter along the nasolabial and nodules are the main clinical features of TE, they have normal skin color and translucent. At present, the pathogenic gene of multiple familial trichoepithelioma( MFT, OMIM 601606) has been identifieding the cylindromatosis gene(CYLD) on chromosome16q12–q13. CYLD gene is a tumor suppressor, which could code the deubiquitinating enzyme. Mutation of CYLD gene leads to the functional defect of the deubiquitinating enzyme, so it would lose the regulation of nuclear factor kappa B( NF-κB), and that would cause NF-κB signal transduction pathway hyperactive. At last, the mutation would make the adnexal tissue of skin excessive proliferate and form tumor. A new CYLD gene mutation report could not only enrich the mutation spectrum, but also provide a favorable condition and platform for genetic counseling, gene diagnosis, prenatal diagnosis and gene therapy in the future. In the study, we collected the clinical data of one pedigree of multiple trichoepithelioma of Han nationality in Sichuan Province, China. The peripheral blood of the patients, healthy family members and 100 unrelated healthy persons were used DNA direct sequencing to detect the mutation of CYLD gene.Objective:Analysis the clinical and genetic features of 1 pedigree with multiple trichoepithelioma of Han nationality in Sichuan Province. And detect the CYLD gene to discover the pathogenic mutations.Methods: Collect the clinical data of the pedigree. Genomic DNA was extracted from peripheral blood of all patients and healthy family members. Polymerase chain reaction(PCR) is used to amplify all the exons of the CYLD gene and its flanking sequences of gene. The products of amplification are sequenced by DNA direct sequencing method, the sequencing results are used to comparative analyse by Chromas 2.0 which could lead to finding out the pathogenic mutation. If the pathogenic mutation was found, then reverse the sequencing.Results: 1) All of patients from one pedigree have normal skin-color, firm papules or nodules which symmetrical distribute along the nasolabial fold. The clinical phenotypes are different. 2) A new missense mutation, c.2273G>A in the patients CYLD gene exon 17 would cause the 758 th arginine transform into glutamine( p.R758Q). The mutation causes 2273 guanine transform into adenine. The mutation could not found in healthy individuals of the family and 100 unrelated healthy person.Conclusion: 1) No significant correlation has been found between clinical phenotype and genotype of the patients with MFT in Han nationality, Sichuan Province. 2) The new missense mutation, c.2273G>A( p.R758Q) may be the pathogenic reason of the family which found out in the pedigree.