Cure GABA-A | Genotype-phenotype correlation&precision treatment of epilesy

The current landscape shows increasing insights into human genetics, yet the translation of genetic data into actionable patient care concepts lags behind. This gap is influenced by two primary challenges: the variability in clinical outcomes associated with different genetic variants within a single gene, complicating treatment decisions, and the empirical nature of current epilepsy treatments due to the absence of targeted therapies for specific genetic changes.

Our specific focus is on the genetic LOF variant D120N in the GABRB3 gene’s beta-3 subunit, known for severe forms of developmental and epileptic encephalopathy (DEE), such as Lennox Gastaut Syndrome (LGS). This variant’s location in the gene’s extracellular region suggests a correlation with clinical severity based on functional domains. However, understanding which genetic variants correlate with mild or severe presentations remains a challenge, impacting prognostication and treatment strategies. Furthermore, the pathophysiology and underlying cellular mechanisms associated with these genetic variants require further investigation.

Through this research, I aim to contribute to the advancement of personalized medicine, ultimately improving outcomes for children affected by genetic epilepsy.