Mutation Analysis of the TSC1and TSC2Genes in Chinese Patients with Tuberous Sclerosis Complex

Background: Tuberous Sclerosis Complex （TSC, OMIM191100） is a rare autosomaldominant neurocutaneous disorder characterized by widespread hamartomas in severalorgans, including the skin, brain, kidney and eye. Population-based studies in Europeanreported a birth rate of1in6000to1in10000. Approximately two-thirds of patients havesporadic mutations. Mutations in either the TSC1gene on chromosome9q34or the TSC2gene on chromosome16p13.3cause TSC. The TSC1and TSC2gene products, hamartinand tuberin respectively, interact to form a protein complex. Until now, more than500TSC1and nearly700TSC2unique allelic variants have been reported but there are noparticular regions within the TSC1or TSC2gene in which mutations occur at a high rate.Objective: To analysis mutations of the TSC1and TSC2genes in patients withtuberous sclerosis complex.Methods: DNA was extracted from blood samples of20patients and200unrelatedhuman controls. Polymerase chain reaction（PCR） and direct sequencing of the TSC1andTSC2gene were performed to identify and confirm the mutations.Results: Nine different mutations, including two deletionmutations（2033delA,1618₁625delTTTTTAGG）,one insertion mutation（1890₁891insT）,three missense mutations（1831C>T,1583T>C,1199T>C）,two non-sense mutations（3094C>T,1513C>T）,one splice mutation（975+1G>T） were identified in these cases.Five of them（2033delA,1890₁891insT,1618₁625delTTTTTAGG,975+1G>T,1583T>C）were novel. No mutation was detected in any of200controls.Conclusion: Five novel mutations of are defined. Our study should be useful for geneticdiagnosis and treatment for the disease.