Genetic analysis of 18 families with tuberous sclerosis complex

AbstractTuberous sclerosis complex (TSC) is mainly caused by variants inTSC1 andTSC2, which encodes hamartin protein and tuberin protein, respectively. Here, we report clinical and molecular characteristics of 18 families with TSC. High-throughput DNA sequencing was employed to detect variants in all the exons and flanking region ofTSC1 andTSC2. TA clone and real-time PCR were performed to verify the pathogenicity of candidate variants. A total of 17 mutations were identified, including 13 mutations inTSC2 and 4 mutations inTSC1. Fifty-six percent (10/18) of the families carried de novo mutations, and 8 of these mutations were not reported previously. Most mutations detected were loss-of-function mutations (15/17). One splice-site mutation (TSC2 c.599  + 5G >  A) caused abnormal splicing and was confirmed by in vitro analysis. Facial angiofibromas (94%) and epilepsy (89%) were the most prevalent clinical features in our patients. Treatment with anti-seizure medication (ASM) or in combination with rapamycin results in clinical remission in most patie nts with TSC-associated seizures (14/15). For genotype–phenotype correlation, patients in our cohort withTSC2 mutations had an earlier onset age and patients withTSC1 showed better response to ASM. Our study has expanded the spectrum ofTSC1 andTSC2 causing TSC.
Source: Neurogenetics - Category: Genetics & Stem Cells Source Type: research