Mutation landscape ofTSC1/TSC2in Chinese patients with tuberous sclerosis complex

Genetic testing ofTSC1andTSC2is important for the diagnosis of tuberous sclerosis complex (TSC), an autosomal dominant neurocutaneous disease. This study retrospectively reviewed 347 samples from patients with clinically suspected TSC being tested for mutations inTSC1andTSC2genes using next-generation sequencing and multiplex ligation-dependent probe amplification. Two hundred eighty-one patients (80.98%) were classified as definite/possible/uncertain diagnosis of TSC and the mutational spectrum ofTSC1/TSC2was described. Two hundred eighteen unique nonsynonymous SNVs/Indels (64 inTSC1, 154 inTSC2) and 13 copy number variants (CNVs) were identified in 241 samples (85.77%), including 82 novel variants. CNVs involving 12 large deletions and one duplication were detected exclusively inTSC2. BothTSC1andTSC2mutations were nearly uniformly distributed in their protein-coding regions. Furthermore, a string of non-TSC1/TSC2deleterious variants in 12 genes was identified in the patients, especially overwhelmingly present in the patients with no mutation identified (NMI) inTSC1/TSC2. Our study provides a comprehensiveTSC1/TSC2mutation landscape and reveal some potential risk non-TSCsvariants present in patients with NMI.

Automated summary

Genetic testing of TSC1 and TSC2 is crucial for diagnosing tuberous sclerosis complex (TSC), revealing a comprehensive mutation landscape in this study. The research also identified potential risk non-TSCs variants present in patients with no mutations detected in TSC1/TSC2.