ArticleNature genetics2015
A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy.
Open access · greenAbstract readComparative Study
In one paragraph
Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers.
0numbers the graph read from it
0cells of the map it votes in
166citing papers in PubMed
21.9field-weighted citation impact, top 1% of its field
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
166 citing papers in PubMed, 313 citations in OpenAlex.
- Article
- An epilepsy-associated KV3.1 potassium channel variant acts via dominant-positive effect.The Journal of general physiology · 2026Article
- Optimization of Pyrazole-Based Activators of Kv3.1.ACS medicinal chemistry letters · 2026Article
- Loss of Function of AFG3L2 Leading to Developmental and Epileptic Encephalopathy.CNS neuroscience & therapeutics · 2026Article
- AProceedings of the National Academy of Sciences of the United States of America · 2026Article
- A novel de Novo KCNC1 mutation (c.1147 C > T) presenting with epilepsy and ADHD: a case report and literature review.BMC neurology · 2026Review
- Generation of aZoological research · 2026Article
- Autosomal dominant Kufs disease in a Georgian adult woman: A case report.Epilepsy & behavior reports · 2025Article
- A CGG Repeat Expansion in CSNK1E Associated with Progressive Myoclonic Epilepsy with Incomplete Penetrance.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Recent advances in the pharmacology of voltage-gated ion channels.Pharmacological reviews · 2025Review
- Pathophysiological Mechanisms Fostering Developmental and Epileptic Encephalopathies (DEE): a Complex Interplay between Genetics, Inflammation and Neurodegeneration.Current neurology and neuroscience reports · 2025Review
- Structural insights into the function, dysfunction and modulation of Kv3 channels.Neuropharmacology · 2025Review
- Common Genomic and Proteomic Alterations Related to Disturbed Neural Oscillatory Activity in Schizophrenia.International journal of molecular sciences · 2025Review
- Kv3 channel agonist ameliorates the phenotype of a mouse model of amyotrophic lateral sclerosis.Acta neuropathologica communications · 2025Article
- Identification of candidate genes associated with bipolar disorder by whole-exome sequencing of a Chinese multi-affected pedigree.BMC psychiatry · 2025Article
- Mapping genetic susceptibility to spontaneous preterm birth: analysis of Utah pedigrees to find inherited genetic factors.American journal of obstetrics and gynecology · 2025Article
- Phenotype-Based Classification of Obstructive Hypertrophic Cardiomyopathy Undergoing Myectomy.JACC. Basic to translational science · 2025Article
- Genetic epilepsies with myoclonic seizures: Mechanisms and syndromes.Epilepsia open · 2025Review
- Article
- The Eastern Association of Electroencephalographers: A Canadian/USA success story.Clinical neurophysiology practice · 2025Review
106 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
51 authors at 20 institutions in 16 countries.
Mikko Muona1] Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland. [2] Folkhälsan Institute of Genetics, Helsinki, Finland. [3] Neuroscience Center, University of Helsinki, Helsinki, Finland. [4] Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.ORCID 0000000209496650
Samuel F BerkovicEpilepsy Research Center, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Leanne M DibbensSchool of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
Karen L OliverEpilepsy Research Center, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Snezana MaljevicDepartment of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Marta A BaylySchool of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
Tarja Joensuu1] Folkhälsan Institute of Genetics, Helsinki, Finland. [2] Neuroscience Center, University of Helsinki, Helsinki, Finland. [3] Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.
Laura CanafogliaDepartment of Neurophysiopathology, C. Besta Foundation Neurological Institute, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
Silvana FranceschettiDepartment of Neurophysiopathology, C. Besta Foundation Neurological Institute, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Milan, Italy.
Roberto MichelucciNeurology Unit, IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy.
Salla Markkinen1] Folkhälsan Institute of Genetics, Helsinki, Finland. [2] Neuroscience Center, University of Helsinki, Helsinki, Finland. [3] Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.
Sarah E HeronSchool of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.
Michael S HildebrandEpilepsy Research Center, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Eva AndermannMontreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Frederick AndermannMontreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
Antonio GambardellaInstitute of Neurology, University Magna Graecia, Catanzaro, Italy.
Paolo Tinuper1] Neurology Unit, IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy. [2] Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Laura Licchetta1] Neurology Unit, IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy. [2] Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.
Ingrid E Scheffer1] Epilepsy Research Center, Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia. [2] Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia. [3] Department of Pediatrics, Royal Children's Hospital, University of Melbourne, Melbourne, Victoria, Australia.
Chiara CriscuoloDepartment of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Naples, Italy.
Alessandro FillaDepartment of Neurosciences, Reproductive Sciences and Odontostomatology, Federico II University, Naples, Italy.
Edoardo Ferlazzo1] Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy. [2] Regional Epilepsy Center, Bianchi-Melacrino-Morelli Hospital, Reggio Calabria, Italy.
Jamil AhmadDepartment of Biotechnology and Informatics, Balochistan University of Information Technology, Engineering and Management Sciences, Quetta, Pakistan.ORCID 0000000203204020
Adeel AhmadDepartment of Medicine, Mayo Hospital, Lahore, Pakistan.
Betul Baykan1] Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. [2] Epilepsy Center (EPIMER), Istanbul University, Istanbul, Turkey.
Edith Said1] Department of Anatomy and Cell Biology, University of Malta, Msida, Malta. [2] Section of Medical Genetics, Mater dei Hospital, Msida, Malta.
Meral TopcuDivision of Pediatric Neurology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Patrizia RiguzziNeurology Unit, IRCCS Institute of Neurological Sciences of Bologna, Bellaria Hospital, Bologna, Italy.
Mary D King1] Department of Neurology, Temple Street Children's University Hospital, Dublin, Ireland. [2] Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
Cigdem OzkaraDepartment of Neurology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey.
Danielle M AndradeDivision of Neurology, Department of Medicine, University of Toronto, Toronto Western Hospital, Krembil Neurosciences Program, Toronto, Ontario, Canada.
Bernt A Engelsen1] Department of Clinical Medicine, University of Bergen, Bergen, Norway. [2] Department of Neurology, Haukeland University Hospital, Bergen, Norway.
Arielle CrespelEpilepsy Unit, Hôpital Gui de Chauliac, Montpellier, France.
Matthias LindenauDepartment of Neurology and Epileptology, Epilepsy Center Hamburg-Alsterdorf, Hamburg, Germany.
Ebba Lohmann1] Department of Neurology and Epileptology, Epilepsy Center Hamburg-Alsterdorf, Hamburg, Germany. [2] Department of Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany. [3] German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
Veronica SalettiDevelopmental Neurology Unit, C. Besta Foundation Neurological Institute, IRCCS, Milan, Italy.
João Massano1] Department of Neurology, Centro Hospitalar São João, Porto, Portugal. [2] Department of Clinical Neurosciences and Mental Health, Faculty of Medicine, University of Porto, Porto, Portugal.ORCID 0000000257917149
Michael PriviteraEpilepsy Center, University of Cincinnati Neuroscience Institute, Cincinnati, Ohio, USA.
Alberto J EspayGardner Center for Parkinson Disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio, USA.
Birgit KauffmannKlinikum Links der Weser, Bremen, Germany.
Michael Duchowny1] Brain Institute, Miami Children's Hospital, Miami, Florida, USA. [2] Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida, USA.
Rikke S Møller1] Danish Epilepsy Centre, Dianalund, Denmark. [2] Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark.
Rachel Straussberg1] Neurogenetic Clinic, Child Neurology Institute, Schneider Children's Medical Center of Israel, Petah Tiqvah, Israel. [2] Sackler School of Medicine, Tel-Aviv University, Ramat Aviv, Israel.
Zaid Afawi1] Sackler School of Medicine, Tel-Aviv University, Ramat Aviv, Israel. [2] Zlotowski Center for Neuroscience, Ben-Gurion University, Beer-Sheva, Israel.
Bruria Ben-Zeev1] Sackler School of Medicine, Tel-Aviv University, Ramat Aviv, Israel. [2] Pediatric Neurology Unit, Edmond and Lilly Safra Children's Hospital, Sheba Medical Center, Ramat-Gan, Israel.
Kaitlin E Samocha1] Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [3] Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [4] Program in Genetics and Genomics, Biological and Biomedical Sciences, Harvard Medical School, Boston, Massachusetts, USA.
Mark J Daly1] Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [3] Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [4] Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Steven Petrou1] Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia. [2] Centre for Neural Engineering, University of Melbourne, Melbourne, Victoria, Australia.
Holger LercheDepartment of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
Aarno Palotie1] Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland. [2] Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [4] Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. [5] Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK. [6] Psychiatric and Neurodevelopmental Genetics Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA. [7] Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Anna-Elina Lehesjoki1] Folkhälsan Institute of Genetics, Helsinki, Finland. [2] Neuroscience Center, University of Helsinki, Helsinki, Finland. [3] Research Programs Unit, Molecular Neurology, University of Helsinki, Helsinki, Finland.
The University of Melbourne · AUInstitute of Neurological Sciences · ITUniversity of Helsinki · FIBroad Institute · USUniversity of South Australia · AUFederico II University Hospital · ITHertie Institute for Clinical Brain Research · DEIstanbul University · TRIstituti di Ricovero e Cura a Carattere Scientifico · ITMagna Graecia University · ITMontreal Neurological Institute and Hospital · CATel Aviv University · ILUniversity of Cincinnati · USBalochistan University of Information Technology, Engineering and Management Sciences · PKFondazione IRCCS Istituto Neurologico Carlo Besta · ITGerman Center for Neurodegenerative Diseases · DEHacettepe University · TRHaukeland University Hospital · NOHôpital Gui de Chauliac · FRHospital de São João · PT
Funding
Wellcome Trust 089062Wellcome Trust 098051
Abstract
Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonic-clonic seizures and ataxia. We sequenced the exomes of 84 unrelated individuals with PME of unknown cause and molecularly solved 26 cases (31%). Remarkably, a recurrent de novo mutation, c.959G>A (p.Arg320His), in KCNC1 was identified as a new major cause for PME. Eleven unrelated exome-sequenced (13%) and two affected individuals in a secondary cohort (7%) had this mutation. KCNC1 encodes KV3.1, a subunit of the KV3 voltage-gated potassium ion channels, which are major determinants of high-frequency neuronal firing. Functional analysis of the Arg320His mutant channel showed a dominant-negative loss-of-function effect. Ten cases had pathogenic mutations in known PME-associated genes (NEU1, NHLRC1, AFG3L2, EPM2A, CLN6 and SERPINI1). Identification of mutations in PRNP, SACS and TBC1D24 expand their phenotypic spectra to PME. These findings provide insights into the molecular genetic basis of PME and show the role of de novo mutations in this disease entity.
Indexed as
Mutation, MissensePoint MutationAmino Acid SequenceAmino Acid SubstitutionAnimalsBase SequenceCarrier ProteinsConserved SequenceExomeFemaleGenes, DominantGTPase-Activating ProteinsHeat-Shock ProteinsHumansMaleMembrane ProteinsCarrier ProteinsGTPase-Activating ProteinsHeat-Shock ProteinsKCNC1 protein, humanMembrane ProteinsNerve Tissue ProteinsPrion ProteinsPrionsPRNP protein, humanSACS protein, humanShaw Potassium ChannelsTBC1D24 protein, human
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.