ArticleHuman molecular genetics2023
ANK2 loss-of-function variants are associated with epilepsy, and lead to impaired axon initial segment plasticity and hyperactive network activity in hiPSC-derived neuronal networks.
Article in Human molecular genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Astrocytic ankyrin-2 enables memory persistence in the mouse hippocampus.Nature communications · 2026Article
- Axon Initial Segment: Structure, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Estradiol modulates neuronal network hyperexcitability in select NDD risk genes.bioRxiv : the preprint server for biology · 2026Article
- Brain and circulating EV proteome signatures in schizophrenia as prognostic markers for age-related dementia.Acta neuropathologica communications · 2026Article
- Longitudinal Characterization of GiantResearch (Washington, D.C.) · 2026Article
- Casomorphine-10 (CM-10) Peptide Orchestrates Circadian and Neurodevelopmental Gene Clusters via δ-Opioid Receptor Signaling: Insights from Transcriptome Analysis with δ-Opioid Receptor-Expressing HEK293 Cells.Life (Basel, Switzerland) · 2025Article
- CRISPR-edited iPSCs reveal BSN gene mutations induce neuronal hyperexcitability via astrocyte lipid accumulation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Glutamatergic and GABAergic Synapses in the Human Spinal Dorsal Horn Revealed With Immunohistochemistry.The Journal of comparative neurology · 2025Article
- Combined genomics and proteomics unveils elusive variants and vast aetiologic heterogeneity in dystonia.Brain : a journal of neurology · 2025Article
- Rest Induces a Distinct Transcriptional Program in the Nervous System of the ExercisedInternational journal of molecular sciences · 2025Article
- Requirements for the neurodevelopmental disorder-associated gene ZNF292 in human cortical interneuron development and function.Cell reports · 2025Article
- Regulation of neuronal ankyrin localization and function by post-translational modifications.Biochemical Society transactions · 2025Review
- Self-limited familial focal epilepsy caused by ANK2 variants: A potentially under-recognized condition.Epilepsia open · 2025Article
- A Mutation in the ANK2 Gene Causing ASD and a Review of the Literature.Molecular genetics & genomic medicine · 2025Review
- Roles of ANK2/ankyrin-B in neurodevelopmental disorders: Isoform functions and implications for autism spectrum disorder and epilepsy.Current opinion in neurobiology · 2025Review
- Exploratory analysis of a Novel RACK1 mutation and its potential role in epileptic seizures via Microglia activation.Journal of neuroinflammation · 2025Article
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
- Overabundant endocannabinoids in neurons are detrimental to cognitive function.bioRxiv : the preprint server for biology · 2024Article
- Early developmental deletion of forebrain Ank2 causes seizure-related phenotypes by reshaping the synaptic proteome.Cell reports · 2023Article
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Authors and funding
31 authors at 15 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo characterize a novel neurodevelopmental syndrome due to loss-of-function (LoF) variants in Ankyrin 2 (ANK2), and to explore the effects on neuronal network dynamics and homeostatic plasticity in human-induced pluripotent stem cell-derived neurons.
methodsWe collected clinical and molecular data of 12 individuals with heterozygous de novo LoF variants in ANK2. We generated a heterozygous LoF allele of ANK2 using CRISPR/Cas9 in human-induced pluripotent stem cells (hiPSCs). HiPSCs were differentiated into excitatory neurons, and we measured their spontaneous electrophysiological responses using micro-electrode arrays (MEAs). We also characterized their somatodendritic morphology and axon initial segment (AIS) structure and plasticity.
resultsWe found a broad neurodevelopmental disorder (NDD), comprising intellectual disability, autism spectrum disorders and early onset epilepsy. Using MEAs, we found that hiPSC-derived neurons with heterozygous LoF of ANK2 show a hyperactive and desynchronized neuronal network. ANK2-deficient neurons also showed increased somatodendritic structures and altered AIS structure of which its plasticity is impaired upon activity-dependent modulation.
conclusionsPhenotypic characterization of patients with de novo ANK2 LoF variants defines a novel NDD with early onset epilepsy. Our functional in vitro data of ANK2-deficient human neurons show a specific neuronal phenotype in which reduced ANKB expression leads to hyperactive and desynchronized neuronal network activity, increased somatodendritic complexity and AIS structure and impaired activity-dependent plasticity of the AIS.
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