Objective: Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by unusual tumor-like growth, termed hamartomas that develop in a variety of tissues and organs. Clinical findings characteristic of TSC include facial angiofibroma, epilepsy and mental retardation. In the last decade, two genes (TSC1 and TSC2) responsible for this disease were identified and both of them are speculated to be a kind of tumor suppressor gene. TSC1 and TSC2 are located on 9q34 and 16p13.3, respectively. This study was designed to detect gene mutations in patients with TSC.
Methods: All the exons of TSC1 and TSC2 were analyzed by using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) in DNA separated from peripheral blood of 28 patients with TSC and 100 normal controls. Of the 28 patients, 17 were male and 11 were female, the age of the patients was 1 - 48 years.
Results: The mutations were not clustered on a particular exon in either of the genes. Four TSC1 mutations found in 28 cases were on exons (1 nonsense, 2 missense and 1 frameshift); 13 mutations were found in TSC2 gene (2 nonsense, 2 frameshift, 1 deletion and 8 missense). Both TSC1 and TSC2 mutations were detected in 2 cases respectively. The same missense mutation (Q654E) was found in 2 unrelated patients. There was no obvious relationship between the location of the mutation and the clinical symptoms.
Conclusion: Mutations found in this study were distributed on various exons and there was no clustering of the mutations, the widespread distribution of TSC1/TSC2 mutations hinders the development of a simple diagnostic test, and the identification of individual mutations does not provide prediction of prognosis.