Mutation Analysis Of TSC1 And TSC2 Genes In Three Chinese Patients With Tuberous Sclerosis Complex

Background Tuberous sclerosis complex(TSC, OMIM 191100)is an autosomal dominant multi-system disorder characterized by the development of multiple hamartomas involving many organs, especially in the brain, skin, heart and kidneys. The estimated incidence of TSC is 1/6000 to 1/10000 in western populations. About two-thirds of the cases are sporadic and appear to represent new mutations. TSC displays genetic heterogeneity, there are two TSC disease genes, TSC1 gene on chromosome 9q34 and TSC2 gene on chromosome 16p13. To date, a total of 150 mutations in the TSC1 gene and 481 mutations in the TSC2 gene have been recorded on The Human Gene Mutation Database. A combination of detection techniques were used, with a mutation detection rate of 80% in patients with definite TSC. Mutations in the TSC2 gene on 16p13.3 are responsible for approximately 50% of familial tuberous sclerosis and 80% of sporadic tuberous sclerosis. The types of mutations in TSC1 gene are mainly point mutation, small deletion and insertion mutation, but gene recombination and large deletion mutations are common in the TSC2 gene. TSC genes participated in mTOR signaling and WNT/β-CATENIN signaling to influence cell proliferation and adhesion. Although most researches on TSC gene mutations were carried out at home and abroad, genotype/phenotype correlations are still unknown. Objective To identify TSC gene mutations in three Chinese patients with TSC. This study will contribute to expand database of TSC genes and further illustrate the extensive diversity of mutational events that led to the different phenotypes of TSC.Methods We collected three Chinese TSC patients and their blood samples. Genomic DNA was extracted from peripheral blood. All the coding exons of TSC1 and TSC2 gene of the three patients and 100 unrelated population-matched controls were amplified by polymerase chain reaction and products analyzed by direct sequencing.Results We identified three mutations c.268C > T (p.Q90X), c. 5227C > T (p. R 1743W) and c.3271₃272insTCCG(p.G1091fs)in TSC2 gene, but were not found in 100 unrelated population-matched control individuals. Two mutations (c.268C>T and c. 5227C >T) in TSC2 gene have been reported in the abroad, which were first reported in China. The mutation(c.3271₃272insTCCG)in TSC2 gene was novel. Conclusions The mutations c.268C > T (p.Q90X), c.5227C > T (p.R1743W) and c.3271₃272ins TCCG(p.G1091fs)in TSC2 gene are the cause of clinical phenotype of the three sporadic cases with TSC.