Correlation between epilepsy and genotype: A large retrospective tuberous sclerosis complex cohort

To describe the first large population (n = 297) with tuberous sclerosis complex (TSC) in China and to examine the relationship between variants (type and location) and epilepsy.

All exons and intron-exon boundaries of TSC1/TSC2 were sequenced with next-generation sequencing, and the distribution of several variants and associations between variant types and epilepsy were investigated.

Epilepsy occurred in 83.5% (248/297) of the individuals. The TSC1/TSC2 gene variant detection rate was 89.6% (266/297). The rate of epilepsy was significantly higher in the TSC2 group than in the TSC1 (p = 0.02) and no mutation identified (NMI) groups (p = 0.0005). TSC2 individuals are more likely to have spasms than TSC1 individuals (p =0.03). The age at epilepsy onset of individuals in the TSC2 group was younger than that of individuals in the TSC1 group (p = 0.008) and NMI group (p = 0.01). The age at epilepsy onset with truncated variants in the TSC1 group was significantly younger than that of individuals with nontruncated variants (p = 0.0001). The rate of epilepsy was significantly higher if variants occurred in the functional domain than in the nonfunctional domain in TSC2 individuals (p = 0.02).

This was the first large cohort study of the Chinese TSC population in which a comparative analysis of genotype and epilepsy was conducted. Individuals with TSC2 variants appeared to have more severe epileptic phenotypes, such as younger age at epilepsy onset, than those with TSC1 variants and NMI, and individuals with variants that occurred in TSC2 functional domains were more prone to epilepsy and had a younger age at epilepsy onset.