Topic: developmental and epileptic encephalopathy

Altered neuronal excitability in neurodevelopmental disorders can have profound implications for adult brain function. Understanding the critical time windows determining the clinical outcomes and lasting changes induced during these periods is therefore crucial. In our mouse model of developmental and epileptic encephalopathy (DEE) harboring a patient-derived Scn2a (p.A263V) mutation that results in a gain-of-function of Nav1.2 channels, Scn2a mutants exhibit a transient increase in excitability of hippocampal pyramidal neurons in vitro during the neonatal period. In vivo, homozygous Scn2a mu

Pathogenic variants in GABAA receptor subunits are a prominent cause of genetic epilepsies. Recent biophysical analysis of pathogenic GABRB3 variants reveals that both loss- and gain-of-function can cause epilepsy. Stratification shows that patients carrying gain-of-function variants experience an earlier onset of seizures that are refractory and have worse developmental delay compared to loss-of-function variant patients. This suggests that distinct pathological mechanisms underlie disease in each GABRB3 functional class. To date, research has only focused on loss-of-function variants. Here,