The de novo GABRA4 p.Thr300Ile variant found in a patient with early-onset intractable epilepsy and neurodevelopmental abnormalities displays gain-of-function traits

Overall, our observations complement the study by Vogel et al.1 and highlight an important role for gain-of-function extrasynaptic receptors in the etiology of epilepsy and neurodevelopmental disorders. The challenge now is to accumulate enough variants in the GABRA4 and GARBD genes to robustly define the clinical phenotype that is associated with distinct functional changes in each gene.