ArticleAnnals of clinical and translational neurology2019
Functional consequences of a KCNT1 variant associated with status dystonicus and early-onset infantile encephalopathy.
Article in Annals of clinical and translational neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 3 of them syntheses that pooled it.
What it found
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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.
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Who cites it
18 citing papers in PubMed, 3 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Efficacy of anti-seizure medications and alternative therapies (ketogenic diet, CBD, and quinidine) in KCNT1-related epilepsy: A systematic review.Epilepsia open · 2024Pooled it
- Analysing an allelic series of rare missense variants of CACNA1I in a Swedish schizophrenia cohort.Brain : a journal of neurology · 2022Pooled it
- Intellectual Disability and Potassium Channelopathies: A Systematic Review.Frontiers in genetics · 2020Pooled it
- Antisense oligonucleotide-mediated knockdown therapy in two infants with severe KCNT1 epileptic encephalopathy.Nature medicine · 2026Article
- Expanding the phenotypic and genotypic spectrum ofBrain communications · 2026Article
- KCNT1 gene variant-associated epilepsy: genetic insights, functional mechanisms, and emerging therapies.Journal of neurology · 2025Review
- Electrophysiological characterization of human KCNT1 channel modulators and the therapeutic potential of hydroquinine and tipepidine in KCNT1 mutation-associated epilepsy mouse model.Acta pharmacologica Sinica · 2025Article
- Structure-Activity Relationship Studies in a Series of 2-Aryloxy-Molecules (Basel, Switzerland) · 2024Article
- Heterozygous expression of aeLife · 2024Article
- Heterozygous expression of abioRxiv : the preprint server for biology · 2024Article
- Structure-Activity Relationship Studies in a Series of Xanthine Inhibitors of SLACK Potassium Channels.Molecules (Basel, Switzerland) · 2024Article
- Epilepsy-associated SCN2A (NaV1.2) variants exhibit diverse and complex functional properties.The Journal of general physiology · 2023Article
- Automated Patch-Clamp and Induced Pluripotent Stem Cell-Derived Cardiomyocytes: A Synergistic Approach in the Study of Brugada Syndrome.International journal of molecular sciences · 2023Review
- Epilepsy-associatedbioRxiv : the preprint server for biology · 2023Article
- KNeurobiology of disease · 2022Article
- Discovery of the First Orally Available, Selective KACS medicinal chemistry letters · 2021Article
- The Functional Properties, Physiological Roles, Channelopathy and Pharmacological Characteristics of the Slack (KCNT1) Channel.Advances in experimental medicine and biology · 2021Review
- A nonlinear and time-dependent leak current in the presence of calcium fluoride patch-clamp seal enhancer.Wellcome open research · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveWe identified a novel de novo KCNT1 variant in a patient with early-infantile epileptic encephalopathy (EIEE) and status dystonicus, a life-threatening movement disorder. We determined the functional consequences of this variant on the encoded K
methodsA retrospective case review of the proband is presented. We performed manual and automated electrophysiologic analyses of the KCNT1-L437F variant expressed heterologously in Chinese hamster ovary (CHO) cells in the presence of channel activators/blockers.
resultsThe KCNT1-L437F variant, identified in a patient with refractory EIEE and status dystonicus, confers a gain-of-function channel phenotype characterized by instantaneous, voltage-dependent activation. Channel openers do not further increase L437F channel function, suggesting maximal activation, whereas channel blockers similarly block wild-type and variant channels. We further demonstrated that KCNT1 current can be measured on a high-throughput automated electrophysiology platform with potential value for future screening of novel and repurposed pharmacotherapies.
interpretationA novel pathogenic variant in KCNT1 associated with early-onset, medication-refractory epilepsy and dystonia causes gain-of-function with rapid activation kinetics. Our findings extend the genotype-phenotype relationships of KCNT1 variants to include severe dystonia.
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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.