ArticleProceedings of the National Academy of Sciences of the United States of America2013
Genotype-phenotype correlations in neonatal epilepsies caused by mutations in the voltage sensor of K(v)7.2 potassium channel subunits.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 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
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 181 citations in OpenAlex.
- Genetic etiologies of the electrical status epilepticus during slow wave sleep: systematic review.BMC genetics · 2018Pooled it
- Molecular Basis for Activation to Inhibition Switching in Kv7.2 Channel Modulators.Angewandte Chemie (International ed. in English) · 2026Article
- RNA-Based Therapeutics in Genetic Neurodevelopmental Disorders: Bridging Molecular Genetics and Precision Medicine.International journal of molecular sciences · 2026Review
- KArchiv der Pharmazie · 2026Review
- Kcnq2 R213 knock-in mice reveal variant- and region-specific mechanisms underlying self-limited familial neonatal-infantile epilepsy and early infantile developmental and epileptic encephalopathy.Acta neuropathologica communications · 2026Article
- Neurodevelopmental features in KCNQ2 developmental and epileptic encephalopathy may have limited associations with KEpilepsia open · 2026Article
- Shared Disease Mechanisms in Neurodevelopmental Disorders: A Cellular and Molecular Biology Perspective.Brain sciences · 2025Review
- Impact of rapid genomic testing on clinical outcomes of acutely unwell children presenting with severe epilepsy.European journal of human genetics : EJHG · 2025Article
- In silico investigation of the puzzling dopamine effects on excitability and synaptic plasticity in hippocampal CA1 pyramidal neurons.Scientific reports · 2025Article
- Electrophysiological Abnormalities and Pharmacological Corrections of Pathogenic Missense Variants in KCNQ3.Neuroscience bulletin · 2025Article
- Kcnq (Kv7) channels exhibit frequency-dependent responses via partial inductor-like gating dynamics.Communications biology · 2025Article
- A case of early epileptic encephalopathy caused by new mutation at W218C inBiochemistry and biophysics reports · 2025Article
- Potassium current inactivation as a novel pathomechanism for KCNQ2 developmental and epileptic encephalopathy.Epilepsia · 2025Article
- Targeting Kv7 Potassium Channels for Epilepsy.CNS drugs · 2025Review
- Constitutive opening of the Kv7.2 pore activation gate causesProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Lipophilic compounds restore function to neurodevelopmental-associated KCNQ3 mutations.Communications biology · 2024Article
- Review
- A small-molecule activation mechanism that directly opens the KCNQ2 channel.Nature chemical biology · 2024Article
- Mathematical models of C-type and N-type inactivating heteromeric voltage gated potassium channels.Frontiers in cellular neuroscience · 2024Article
- A realistic computational model for the formation of a Place Cell.Scientific reports · 2023Article
36 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Mutations in the K(V)7.2 gene encoding for voltage-dependent K(+) channel subunits cause neonatal epilepsies with wide phenotypic heterogeneity. Two mutations affecting the same positively charged residue in the S4 domain of K(V)7.2 have been found in children affected with benign familial neonatal seizures (R213W mutation) or with neonatal epileptic encephalopathy with severe pharmacoresistant seizures and neurocognitive delay, suppression-burst pattern at EEG, and distinct neuroradiological features (R213Q mutation). To examine the molecular basis for this strikingly different phenotype, we studied the functional characteristics of mutant channels by using electrophysiological techniques, computational modeling, and homology modeling. Functional studies revealed that, in homomeric or heteromeric configuration with K(V)7.2 and/or K(V)7.3 subunits, both mutations markedly destabilized the open state, causing a dramatic decrease in channel voltage sensitivity. These functional changes were (i) more pronounced for channels incorporating R213Q- than R213W-carrying K(V)7.2 subunits; (ii) proportional to the number of mutant subunits incorporated; and (iii) fully restored by the neuronal K(v)7 activator retigabine. Homology modeling confirmed a critical role for the R213 residue in stabilizing the activated voltage sensor configuration. Modeling experiments in CA1 hippocampal pyramidal cells revealed that both mutations increased cell firing frequency, with the R213Q mutation prompting more dramatic functional changes compared with the R213W mutation. These results suggest that the clinical disease severity may be related to the extent of the mutation-induced functional K(+) channel impairment, and set the preclinical basis for the potential use of K(v)7 openers as a targeted anticonvulsant therapy to improve developmental outcome in neonates with K(V)7.2 encephalopathy.
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.