Investigation of novel de novo KCNC2 variants causing severe developmental and early-onset epileptic encephalopathy

•We presented two individuals with severe developmental delay and epileptic encephalopathy due to de novo variants in the KCNC2 gene.•Functional experiments showed that all three variants (including a previously reported variant) caused significantly slowing of gating kinetics of Kv3.2 channel.•Modeling experiments in GABAergic interneurons revealed that all variants obviously reduced cell firing frequency, indicating a disinhibition of GABAergic system caused by net loss-of-function effect of the variants.