Two mutations in TRPM3 resulting in developmental and epileptic encephalopathies result in a gain-of-channel function, which may lie at the basis of epileptic activity and neurodevelopmental symptoms in the patients.

Variants in FGF13, associated with developmental and epileptic encephalopathies, alter neuronal excitability by affecting inhibitory neurons and by a sodium channel-independent mechanism.

Two genetic mouse models for HCN1-linked developmental epileptic encephalopathy display distinct biophysical changes in HCN1 ion channel properties but similar worsening of seizures in response to antiepileptic drugs, thereby recapitulating key features of the human disease.

EncoreDNM identifies abundant enrichment correlations across disorders for de novo mutations.

Two genetically distinct Stxbp1 haploinsufficiency mouse models exhibit seizures and impairments in cognitive, psychiatric, and motor functions, representing robust preclinical models of STXBP1 encephalopathy with both construct and face validity.

Two novel mutations in the GRIN2B gene reduce glutamate affinity by >1000-fold, reduce the receptors proton-sensitivity, and exert a dominant-negative effect over receptors in neurons.

Proteomic analysis of brain organoids from creatine transporter deficiency (CTD) patients enhance the understanding of CTD offering potential therapeutic targets and a robust foundation for continued research in the field.

Disease-associated mutants of the TRPM3 ion channel are overactive, and they are inhibited by the antiepileptic medication primidone, offering a potential therapeutic intervention to treat this channelopathy.

A single amino acid change in a neuronal ion channel called KCNQ2 blocks ion flow, prevents protein localization on axons, and results in severe epilepsy and slowed neurological development.

Loss-of-function mutations in human genes are an important class of disease causing variation, and estimates of their effects on evolutionary fitness can be used to evaluate their pathogenicity.