Detection Of Gene Mutations And Clinical Analysis Of Tuberous Sclerosis Complex

Background Tuberous sclerosis complex(TSC)is an autosomal dominant multisystem disease with an incidence of 1/6000-10000.There is no racial difference in TSC.The clinical manifestations of TSC depend on many factors such as age,gender and the type of genetic mutation.It is characterized by hamartoma in multiple organs or systems,particularly in nervous system manifestations such as epilepsy,autism and cognitive dysfunction.Study have shown that it was caused by abnormal activation of the mammalian target of rapamycin(m TOR)pathway due to the mutations in the TSC1 and TSC2 genes.About 75%-80% of TSC patients were detected mutations in the pathogenic gene,though 15% of patients were not detected mutations.To date,many TSC mutation sites have been found.But the critical region of mutation has not been observed.Objectives This study was designed to analyze the mutation of pathogenic gene in three sporadic patients with TSC,in order to enrich the mutation spectrum of the disease and provide a theoretical basis for the analysis of genotypes and phenotypes.In addition,this study analyzed the clinical characteristics and the motivation of treatment in 42 TSC patients.The pathogenesis,early diagnosis,treatment,targeted monitoring and management of TSC have been further understood.Methods1.Mutational detection of TSC1 and TSC2 gene was performed in three sporadic cases with Sanger sequencing.2.Refer to the electronic cases in our hospital from January 2003 to December 2019,42 confirmed TSC cases with complete clinical data were included.The clinical manifestations,the motivation of treatment and other relevant data were analyzed by Chi-square test and Fisher's exact probability method.The P <0.05 was considered to be statistically significant.Results1.The study identified a missense mutation c.1960C>G(p.Q654E)in case 1.A missense mutation c.965T>C(p.M322T)and a synonymous mutation c.1335A>G(p.E445E)were detected in case 3.And no mutation of the TSC pathogenic gene was detected in case 2.2.18 male patients and 24 female patients were collected.The main clinical manifestations were epilepsy in 35 cases(83.33%),facial angiofibroma in 24 cases(57.14%)and subependymal nodules in 23 cases(54.76%).There are 33 cases(78.57%)went to hospital to treat for epilepsy.And so as renal angiomyolipoma in 17 cases(40.48%),skin lesions in 3 cases(7.14%).3.Among the patients with epilepsy,18 were male and 17 were female(P = 0.014).Among the patients with facial angiofibroma,7 were male and 17 were female(P = 0.038).In addition,patients with treatment motivation of renal angiomyolipoma were all female(P = 0.029).Conclusions This study identified the mutation sites in 2 cases.And in case 2,no mutation of TSC1 and TSC2 gene was detected.It was necessary to combine clinical manifestations and the results of gene mutation detection in the diagnosis.Some differences in gender of TSC were observed.Especially in some clinical manifestations and treatment motivation.Epilepsy is more common in men,facial angiofibroma is more common in women.And female patients are more likely to see a doctor for the first time because of renal angiomyolipoma.