ArticleBiological psychiatry2021
Hyperexcitable Phenotypes in Induced Pluripotent Stem Cell-Derived Neurons From Patients With 15q11-q13 Duplication Syndrome, a Genetic Form of Autism.
Article in Biological psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Neural excitation/inhibition imbalance and neurodevelopmental pathology in human copy number variant syndromes: a systematic review.Journal of neurodevelopmental disorders · 2025Pooled it
- Astrocytes in Genetic Epilepsies: Supporting Actor or Key Player?Journal of neuroscience research · 2026Review
- Distinct synaptic mechanisms underlie NRXN1 variant and disorder background-dependent phenotypes in iPSC-derived neurons.Cell reports · 2026Article
- How copy number variations shape brain developmental disorders: Unraveling the synaptic puzzle.Psychiatry and clinical neurosciences · 2026Review
- Review
- The Interplay of Oxidative Stress, Mitochondrial Dysfunction, and Neuroinflammation in Autism Spectrum Disorder: Behavioral Implications and Therapeutic Strategies.Brain sciences · 2025Review
- Distinct Synaptic Mechanisms DrivebioRxiv : the preprint server for biology · 2025Article
- Dysfunctional sodium channel kinetics as a novel epilepsy mechanism in chromosome 15q11-q13 duplication syndrome.Epilepsia · 2023Article
- Early maturation and hyperexcitability is a shared phenotype of cortical neurons derived from different ASD-associated mutations.Translational psychiatry · 2023Article
- The role of UBE3A in the autism and epilepsy-related Dup15q syndrome using patient-derived, CRISPR-corrected neurons.Stem cell reports · 2023Article
- Duplication Versus Deletion Through the Lens of 15q13.3: Clinical and Research Implications of Studying Copy Number Variants Associated with Neuropsychiatric Disorders in Induced Pluripotent Stem Cell-Derived Neurons.Stem cell reviews and reports · 2023Review
- Review
- Unraveling pathological mechanisms in neurological disorders: the impact of cell-based and organoid models.Neural regeneration research · 2022Review
- Molecular and behavioral consequences of Ube3a gene overdosage in mice.JCI insight · 2022Article
- Development of a platform to investigate long-term potentiation in human iPSC-derived neuronal networks.Stem cell reports · 2022Article
- Loss of function of OTUD7A in the schizophrenia- associated 15q13.3 deletion impairs synapse development and function in human neurons.American journal of human genetics · 2022Article
- Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2022Review
- Modeling Epilepsy Using Human Induced Pluripotent Stem Cells-Derived Neuronal Cultures Carrying Mutations in Ion Channels and the Mechanistic Target of Rapamycin Pathway.Frontiers in molecular neuroscience · 2022Review
- Human stem cell-based models for studying autism spectrum disorder-related neuronal dysfunction.Molecular autism · 2020Review
- Human in vitro models for understanding mechanisms of autism spectrum disorder.Molecular autism · 2020Review
Corrections and comments
- Commented on by
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundChromosome 15q11-q13 duplication syndrome (Dup15q) is a neurogenetic disorder caused by duplications of the maternal copy of this region. In addition to hypotonia, motor deficits, and language impairments, patients with Dup15q commonly meet the criteria for autism spectrum disorder and have a high prevalence of seizures. It is known from mouse models that synaptic impairments are a strong component of Dup15q pathophysiology; however, cellular phenotypes that relate to seizures are less clear. The development of patient-derived induced pluripotent stem cells provides a unique opportunity to study human neurons with the exact genetic disruptions that cause Dup15q.
methodsHere, we explored electrophysiological phenotypes in induced pluripotent stem cell-derived neurons from 4 patients with Dup15q compared with 6 unaffected control subjects, 1 patient with a 15q11-q13 paternal duplication, and 3 patients with Angelman syndrome.
resultsWe identified several properties of Dup15q neurons that could contribute to neuronal hyperexcitability and seizure susceptibility. Compared with control neurons, Dup15q neurons had increased excitatory synaptic event frequency and amplitude, increased density of dendritic protrusions, increased action potential firing, and decreased inhibitory synaptic transmission. Dup15q neurons also showed impairments in activity-dependent synaptic plasticity and homeostatic synaptic scaling. Finally, Dup15q neurons showed an increased frequency of spontaneous action potential firing compared with control neurons, in part due to disruption of KCNQ2 potassium channels.
conclusionsTogether, these data point to multiple electrophysiological mechanisms of hyperexcitability that may provide new targets for the treatment of seizures and other phenotypes associated with Dup15q.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.