Diagnosis Of Patients With Tuberous Sclerosis Complex By Direct Sequencing And MLPA

Backgrounds:Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by hamartomas in multiple organ systems, including the brain, skin, heart and kidneys. Sometimes, lung, bones and some endocrine glands are involved as well. The typical symptoms in patients are facial sebaceous tumors, localized skin lesions, seizures, mental retardation and multiple hamartomas. And phenotypic differences between different patients range from mild to severe. The epidemiological investigation in western speculated that the TSC incidence rate in birth was1/6000, and the male to female ratio was about2-3:1. About2/3of the TSC cases are sporadic, suggesting there is a high spontaneous mutation rates. Currently two disease-related genes, TSC1(MIM#60528) and TSC2(MIM#191092) were identified.Purpose:The purpose of the current research was to detect the underlying genetic defect in probands, and perform prenatal genetic diagnosis for them or their parents’current pregnancy or re-pregnancy.Methods:Totally, all the patients with clinical diagnosis were studied depending on Multiplex Ligation-dependent Probe Amplification (MLPA) and specific PCR sequencing analysis of TSC1and TSC2gene mutations.Results:We have survey the mutation of TSC1and TSC2from16Chinese patients with tuberous sclerosis complex. A total of15cases including one TSC1mutation (SNP) and fourteen TSC2mutations (including one SNP and one synonymous mutation) were identified. The13pathogenic mutations consists of11point-mutation and2large-deletion mutations,4TSC2mutations have not been described previously. Conclusion:MLPA is a highly sensitive and accurate detection method for large deletion/duplication. Combining direct sequencing with MPLA can detect tuberous sclerosis fast and accurately, which also increases the detection rate.