Multiple Trichoepithelioma Disease Gene Mapping And Cloning

Multiple familial trichoepithelioma is a skin adnexal tumor, presenting many nodules and papules on the face, which tends to affect patients before adolescence. The disease is regarded as a benign tumor in clinical diagnose although some cases are reported that the disease can mutate malignant tumor. It is considered as autosomal dominant disease in heredity. There is still no effective cure for multiple familial trichoepithelioma because mechanism of the disease is still unknown. In this study, we collected blood samples from three Chinese families with multiple familial trichoepithelioma. Locus of the disease was mapped to 16q12-13 through whole genome scan and linkage analysis. In this region, some candidate genes were confirmed by expression and function screening. Some mutations were detected for the CYLD gene in the three families. In family I, a single nucleotide deletion was found in CDS 1462 causing a frame-shift. As family II, a transition from cytidine to thymidine was showed in CDS 2128 resulting in a nonsense mutation. While in family III, a missense mutation was caused by substitution of an adenosine with a thymidine in CDS 2822. We successfully identified the disease gene for multiple familial trichoepithelioma through mutation analysis. In order to reveal mechanism of the disease, with consent of patients we collected tumor samples and carried out loss of heterozygosis analysis. Results of the analysis demonstrated that mechanism of the disease follows a two-hit model. This finding provides some basis for studying the mechanism and finding a cure of the disease.