Human iPSC-derived glutamatergic neurons with pathogenic KCNQ2 variants display hyperactive bursting phenotypes.

ABSTRACT: Pathogenic variants in the KCNQ2 gene, which encodes a potassium channel subunit, are associated with neonatal seizures, epileptic encephalopathy, intellectual disability, and autism. Although the consequences of disrupted KCNQ2 channel function have been studied in the past, the detailed molecular mechanisms underlying the development of neurological phenotypes remain unclear, and neuronal models of specific patient variants are lacking. We generated patient-specific induced pluripotent stem cells (iPSCs) from fibroblasts from three individuals with distinct KCNQ2 pathogenic variants. We corrected the KCNQ2 variants using CRISPR-Cas9 editing to create isogenic controls and differentiated these iPSCs into glutamatergic neurons to study the effects of each variant on neuronal function. The

SUBMITTER: Sundberg M 

PROVIDER: S-EPMC12745820 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature