Novel Genetic Insights into Lateral Temporal Lobe Epilepsy: Findings from Whole Exome Sequencing

Lateral temporal lobe epilepsy (LTLE) is characterized by auditory auras and is often associated with genetic factors. Previous studies have identified various genes linked to LTLE, including LGI1. However, there remains a need to explore other genetic variants that contribute to the LTLE phenotype, particularly in the absence of LGI1 mutations.

A cohort followed in our epilepsy center and diagnosed as LTLE with auditory aura was recruited to the study. We have performed whole exome sequencing data analysis of 19 patients using a two-step approach. In the first step, we have focused on six LTLE associated genes, namely LGI1, RELN, MICAL1, CNTNAP2, DEPDC5 and SCN1A. In the second step, the data was filtered against a list of epilepsy related genes.

Our analysis identified novel variants in LTLE-associated genes, including RELN, SCN1A, and CNTNAP2, which confirmed previous findings. Importantly, for the first time, we identified a loss-of-function variation in the CHRNB2 gene that may be associated with the LTLE phenotype.

Our study underscores the genetic heterogeneity of lateral temporal lobe epilepsy (LTLE) by identifying new genetic variants linked to the disorder. Notably, we propose that CHRNB2 is a novel gene associated with LTLE, thereby broadening the spectrum of known genetic contributors. This finding highlights the complexity of LTLE's genetic landscape and suggests new pathways for future research and clinical application.