biostudies-literatureBhat SNatural Sciences and Engineering Research Council of CanadaFonds de recherche du Quebec SanteEpilepsy SocietyCanadian Institutes of Health ResearchOntario Research FoundationChildren's Hospital of Eastern Ontario FoundationNIHR University College London Hospitals Biomedical Research CentreGénome QuébecGenome AlbertaNIHR Great Ormond Street Hospital Biomedical Research CentreGenome British ColumbiaOntario Genomics InstituteGenome CanadaDigital Research Alliance of Canada761-777https://www.ebi.ac.uk/biostudies/studies/S-EPMC11023922biostudies-literatureUnknown111(4)Ion channels mediate voltage fluxes or action potentials that are central to the functioning of excitable cells such as neurons. The KCNB family of voltage-gated potassium channels (Kv) consists of two members (KCNB1 and KCNB2) encoded by KCNB1 and KCNB2, respectively. These channels are major contributors to delayed rectifier potassium currents arising from the neuronal soma which modulate overall excitability of neurons. In this study, we identified several mono-allelic pathogenic missense variants in KCNB2, in individuals with a neurodevelopmental syndrome with epilepsy and autism in some individuals. Recurrent dysmorphisms included a broad forehead, synophrys, and digital anomalies. Additionally, we selected three variants where genetic transmission has not been assessed, from two epilAmerican journal of human geneticsMono-allelic KCNB2 variants lead to a neurodevelopmental syndrome caused by altered channel inactivation.PMC11023922RGPIN-2023-04752OGI-147PJT-169160Louie RJHughes SSStoler JMCampeau PMDubourg CRousseau JBhat SKoboldt DCSisodiya SMMichaud CHoytema van Konijnenburg EMMLourenco CMClarkson LKLichty ADemurger FBlunck Rvan Hasselt PMAccogli ASullivan BRThiffault ISrour MReshmi SCKoop KTremblay ESfalseMono-allelic KCNB2 variants lead to a neurodevelopmental syndrome caused by altered channel inactivation.Ion channels mediate voltage fluxes or action potentials that are central to the functioning of excitable cells such as neurons. The KCNB family of voltage-gated potassium channels (Kv) consists of two members (KCNB1 and KCNB2) encoded by KCNB1 and KCNB2, respectively. These channels are major contributors to delayed rectifier potassium currents arising from the neuronal soma which modulate overall excitability of neurons. In this study, we identified several mono-allelic pathogenic missense variants in KCNB2, in individuals with a neurodevelopmental syndrome with epilepsy and autism in some individuals. Recurrent dysmorphisms included a broad forehead, synophrys, and digital anomalies. Additionally, we selected three variants where genetic transmission has not been assessed, from two epil2024-01-01T00:00:00Z2024 Apr2026-06-03T07:12:21.048Z2025-04-04T08:21:43.928ZS-EPMC110239223850329910.1016/j.ajhg.2024.02.014