Preliminary Identification Of Causative Gene For Tuberous Sclerosis Complex

Background: Tuberous sclerosis complex(TSC)is a neurocutaneous syndrome of autosomal dominant disorder,which is associated with hamartoma formation on multiple organ systems.The lesions are often formed in embryonic period.Its significant clinical features are facial sebaceous adenoma,seizures and cognitive disabilities.The causative mutations of the disease are mainly lie in two genes: TSC1 and TSC2,respectively encoding the protein hamartin and tuberin.But,15% causative mutations of TSC are unknown.The pathogenesis is related to the activity of m TOR pathway and the continuous excitatory of m TOR pathway is the molecular basis of TSC.Antagonism of the m TOR pathway with rapamycin may provide therapeutic options for TSC patients.Objective: We use whole exome sequencing(WES)technology in the familial patients with tuberous sclerosis complex(TSC)in order to find causative mutation,and the sanger sequencing method was used to verify the causative genes.Methods: All the family members were examined through detailed clinical evaluations,auxiliary examinations and CT,et al.Then blood samples from six family members were prepared,and were analyzed by whole exome sequencing,a new generation of high-throughput exome sequencing method.The single nucleotide polymorphisms(SNPs)were screened by using the database,such as db SNP and HAPMAP,and then the candidate genes were selected to select the candidate genes.Genes was analyzed,and finally screening out the most likely mutation sites.In the end,the results were examined by Sanger sequencing.Results: No causative mutation for the familial tuberous sclerosis complex was found with whole exome sequencing technology.Conclusion: No causative mutation for the familial tuberous sclerosis complex locate in exome sequence of TSC1 and TSC2.