Identification Of Novel TSC2 Mutations In Patients With Tuberous Sclerosis Complex

Background Tuberous sclerosis complex ( TSC ) is an autosomal dominant, multisystem disorder characterized by the development of multiple hamartomas involving many organs, especially the brain, skin, heart and kidneys. It was first described by Von Recklinghauson in 1862 and was first designated by Bourneville in 1880, therefore we also call it Bourneville disease. The clinical manifestations of TSC vary widely, even within families. The estimated incidence of TSC is one in 6000 -10,000 live births in western populations.About two-thirds of the cases are sporadic and appear to represent new mutations. TSC displays genetic heterogeneity with two known genes: TSC1 and TSC2, which was cloned in 1997 and 1993 respectively. To date, a total of 135 mutations in the TSCl gene and 389 mutations in the TSC2 gene have been recorded on The Human Gene Mutation Database, most of which were reported in America, Europe and Japan.Mutations are distributed throughout the coding sequence without a specific hot spot .Other than TSC2/PKD1 contiguous gene deletions and significant renal cystic disease with progressive renal failure, no genotype/phenotype correlation has been described within each gene. We carried out mutation scanning in TSC patients by direct sequencing of PCR products and analyzed the clinical and genetic features of TSC in Chinese.Objectives To identify gene mutations in Chinese patients with TSC and to delineate the clinical and genetic features of Chinese TSC cases by a literature review.Methods We directly performed mutation detection both the TSC genes in 1 Chinese multi-generation family and 1 sporadic case with TSC by direct sequencing of PCR products and reviewed all papers about TSC mutations of Chinese origin reported since 1994 using the Chinese Biology Medicine (CBM) disk and PubMed.Results We identified two novel mutations of TSC2, c.3099delC ( p.Y1033fs ) and .4420₄424delAGAGT (p.R1474fs) .20 cases with TSC mutation of Chinese...