Variable Expression of GABAA Receptor Subunit Gamma 2 Mutation in a Nuclear Family Displaying Developmental and Encephalopathic Phenotype.

Mutations in GABA receptor subunit genes () are a major etiology for developmental and epileptic encephalopathies (DEEs). This article reports a case of a genetic abnormality in and updates the pathophysiology and treatment development for mutations in DEEs based on recent advances. Mutations in , especially in , , , and , impair GABAergic signaling and are frequently associated with DEEs such as Dravet syndrome and Lennox-Gastaut syndrome, as GABAergic signaling is critical for early brain development. We here present a novel association of a microdeletion of with a diagnosed DEE phenotype. We characterized the clinical phenotype and underlying mechanisms, including molecular genetics, EEGs, and MRI. We then compiled an update of molecular mechanisms of mutations, especially the mutations in and attributed to DEEs. Genetic therapy is also discussed as a new avenue for treatment of DEEs through employing antisense oligonucleotide techniques. There is an urgent need to define treatment targets and explore new treatment paradigms for the DEEs, as early deployment could alleviate long-term disabilities and improve quality of life for patients. This study highlights biomolecular targets for future therapeutic interventions, including via both pharmacological and genetic approaches.