Genetype And Clinical Phenotype Analysis In A Cohort Of43Chinese Patients With Tuberous Sclerosis Complex

Objective To detect the pathogenic mutations of both TSC1and TSC2genes in43Chinese probands with tuberous sclerosis complex and analyse the correlations of genotype andclinical phenotype. Method Standard clinical evaluation was performed on each proband andtheir family mambers. Entire coding exons and intron-exon boundaries of TSC1and TSC2geneswere screened in the probands with direct sequencing. Furthermore, the correlations of thegenotype and clinical phenotype were analysed retrospectively. Result Disease-causingmutations were identified in a total of32probands (32/43,74.4%), including7TSC1mutations(5sporadic and2familial cases) and25TSC2mutations (23sporadic and2familial cases). Theratio of TSC2: TSC1mutations was3.6:1. A broad spectrum of pathogenic mutations has beenidentified at both TSC loci, including frameshift mutation, missense mutation, nonsensemutation, splice site mutation and in-frame mutation. In the cohort of our study, we identified11of32pathogenic mutations and8polymorphic sites which have not been reported previously. Inaddition, we don’t detect any missense mutation at TSC1loci and we don’t find any “hotspot”for mutations of both TSC1and TSC2genes. Consistent with the findings of previous largestudies, the clinical severity of patenet with TSC may range from a mild clinical features tolife-threatening. Overall, comparison of the patients with TSC1mutation, the patients with TSC2mutation may have more severe phenotypes; comparison of the patients who have either a knownTSC1or TSC2pathogenic mutation; the patients with no mutation identified(NMI) may haveless severe phenotypes. Conclusion Our data provide some insight into the genetics and clinicalphenotypic characters of chinese patients with tuberous sclerosis complex. The patients with aTSC2mutation may have higher number and/or severity of clinical manifestations and moremedical monitoring and intervention are needed for these patients. Objective To explore the clinical management of renalangiomyolipoma (AML) associated with tuberous sclerosis complex(TSC). MethodsThe medical records of a27-year-old woman with a known history of TSC was analysedretrospectively and related literatures were learnt. Asymptomatic AML was detectedin her bilateral kidney accidentally by abdomen ultrasonography after her clinicaldiagnosis was confirmed14months. On abdomen CT scan, the largest mass waslocated in the upper pole of right kidney with the diameter size of7.9cm×6.1cm andthe tend of exophytic growth was noted, contrast enhanced CT showed the value ofarterial phase and enhanced phase were136HU and99HU, respectively. At the sametime, the fat densities (<18HU) within mass also was observed, conformed thediagnosis of AML. The parameters of blood routine and Serum creatinine and urea of renalfunction were normal. Accordingly, preventive surgical intervention was performed andthe regular clinical follow-up was carried out. Result The patient underwent thenephron-sparing surgery (NSS) of right kidney in our hospital, report of pathologysupported the type of classic AML. No renal dysfunction, hematuria, flank pain orother surgical complications was observed during our follow-up for6mounths.Supplementary, the pathogenic mutation(TSC2c.2713C>T, p.Arg905Trp) of thepatient and her affected son was identified with direct sequencing. ConclusionLong-term follow up and timely surgical intervention are needed for some TSCpatients with huge renal AML.