ArticleAmerican journal of human genetics2019
Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.
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Article in American journal of human genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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39citing papers in PubMed, 1 pooled it
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- N-Type Ca Channel in Epileptic Syndromes and Epilepsy: A Systematic Review of Its Genetic Variants.International journal of molecular sciences · 2023Pooled it
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- In-depth characterization of the CaScientific reports · 2026Article
- Data-Driven Insights into Hyperkinetic Disorders in Neurodevelopmental Syndromes and Epileptic Encephalopathies.Movement disorders clinical practice · 2026Review
- Movement Disorders in Developmental and Epileptic Encephalopathies.Movement disorders clinical practice · 2026Review
- A novel mutation inFrontiers in neuroscience · 2026Article
- Evaluation, Diagnosis, and Treatment of Concomitant Movement Disorders in Genetic Epilepsies.Epilepsy currents · 2025Review
- A new association between Kleefstra syndrome and Panayiotopoulos epilepsy.Italian journal of pediatrics · 2025Article
- Inactivation of CaV1 and CaV2 channels.The Journal of general physiology · 2025Review
- Calcium Ions in the Physiology and Pathology of the Central Nervous System.International journal of molecular sciences · 2024Review
- Voltage-gated calcium channels in genetic epilepsies.Journal of neurochemistry · 2024Review
- Developmental and epileptic encephalopathies.Nature reviews. Disease primers · 2024Review
- Clinical features and genetic analysis of developmental and epileptic encephalopathy caused by biallelic variants ofHeliyon · 2024Article
- Identification of a de novo CACNA1B variant and a start-loss ADRA2B variant in paroxysmal kinesigenic dyskinesia.Heliyon · 2024Article
- The Interplay Between Splicing of Two Exon Combinations Differentially Affects Membrane Targeting and Function of Human CaFunction (Oxford, England) · 2024Article
- Functional implications of paralog genes in polyglutamine spinocerebellar ataxias.Human genetics · 2023Review
- Ion channels in neurodevelopment: lessons from the Integrin-KCNB1 channel complex.Neural regeneration research · 2023Article
- Ion Channel Genes in Painful Neuropathies.Biomedicines · 2023Review
- Whole-Genome Sequencing Among Kazakhstani Children with Early-Onset Epilepsy Revealed New Gene Variants and Phenotypic Variability.Molecular neurobiology · 2023Article
- Generalised dystonic presentation of CACNA1B-associated dystonia and its response to Levodopa.Acta neurologica Belgica · 2023Article
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Authors and funding
34 authors at 20 institutions in 7 countries.
Kathleen M GormanMolecular Neurosciences, Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK; Department of Neurology, Great Ormond Street Hospital, London WC1N 3JH, UK.
Esther MeyerMolecular Neurosciences, Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.
Detelina GrozevaDepartment of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 OXY, UK; Division of Psychological Medicine and Clinical Neuroscience, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK.
Egidio SpinelliEpilepsy Center, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
Amy McTagueMolecular Neurosciences, Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK; Department of Neurology, Great Ormond Street Hospital, London WC1N 3JH, UK.
Alba Sanchis-JuanDepartment of Haematology, University of Cambridge, NHS Blood and Transplant Centre, Cambridge CB2 0PT, UK; NIHR BioResource, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge CB2 0QQ UK.
Keren J CarssDepartment of Haematology, University of Cambridge, NHS Blood and Transplant Centre, Cambridge CB2 0PT, UK; NIHR BioResource, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge CB2 0QQ UK.
Emily BryantEpilepsy Center, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA; Division of Genetics, Birth Defects and Metabolism, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA.
Adi ReichGeneDx, Gaithersburg, MD 20877, USA.
Amy L SchneiderEpilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg 3084, VIC, Australia.
Ronit M PresslerDepartment of Clinical Neurophysiology, Great Ormond Street Hospital, London WC1N 3JH, UK; Clinical Neurosciences, Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK.
Michael A SimpsonDivision of Genetics and Molecular Medicine, King's College, London WC2R 2LS, UK.
Geoff D DebelleDepartment of General Paediatrics, Birmingham Children's Hospital, Birmingham B4 6NH, UK.
Evangeline WassmerDepartment of Paediatric Neurology, Birmingham Children's Hospital, Birmingham B4 6NH, UK.
Jenny MortonWest Midlands Regional Clinical Genetics Service and Birmingham Health Partners, Birmingham Women's and Children's NHS Foundation Trust, Birmingham B15 2TG, UK.
Diana SieciechowiczEpilepsy Center, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA; Departments of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Eric Jan-KamsteegDepartment of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, Netherlands.
Alex R PaciorkowskiDepartment of Neurology, Pediatrics and Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA.
Mary D KingDepartment of Neurology and Clinical Neurophysiology, Children's University Hospital, Temple Street, Dublin DO1 YC67, Ireland; Academic Centre on Rare Diseases, School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland.
J Helen CrossDepartment of Neurology, Great Ormond Street Hospital, London WC1N 3JH, UK; Departments of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Annapurna PoduriEpilepsy Genetics Program, Department of Neurology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Neurology, Harvard Medical School, Boston, MA 02115, USA.
Heather C MeffordDivision of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, WA 98195, USA.
Ingrid E SchefferEpilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, Heidelberg 3084, VIC, Australia; Florey Institute and Murdoch Institute of Neuroscience and Mental Health, Parkville, 3052, VIC, Australia; Department of Paediatrics, Royal Children's Hospital, University of Melbourne, Parkville, 3052, VIC, Australia.
Tobias B HaackInstitute of Medical Genetics and Applied Genomics, University of Tübingen, Tübingen 72706, Germany.
Gary McCullaghDepartment of Neurology, Royal Manchester Children's Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester M13 9WL, UK.
Deciphering Developmental Disorders StudyDDD Study, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
UK10K ConsortiumUK10K, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
NIHR BioResourceNIHR BioResource, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge CB2 0QQ UK.
John J MillichapDivision of Psychological Medicine and Clinical Neuroscience, MRC Centre for Neuropsychiatric Genetics and Genomics, School of Medicine, Cardiff University, Cardiff, UK; Departments of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA; Ken and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Gemma L CarvillKen and Ruth Davee Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Jill Clayton-SmithManchester Centre for Genomic Medicine, St Mary's Hospital, Manchester University Hospitals, NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester M13 9WL, UK; Division of Evolution and Genomic Sciences, School of Biological Sciences, University of Manchester, Manchester M13 9NT, UK.
Eamonn R MaherDepartment of Medical Genetics, University of Cambridge and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
F Lucy RaymondDepartment of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 OXY, UK; NIHR BioResource, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge CB2 0QQ UK.
Manju A KurianMolecular Neurosciences, Developmental Neurosciences, UCL Great Ormond Street Institute of Child Health, London WC1N 1EH, UK; Department of Neurology, Great Ormond Street Hospital, London WC1N 3JH, UK. Electronic address: manju.kurian@ucl.ac.uk.
Northwestern University · USUniversity of Cambridge · GBGreat Ormond Street Hospital · GBKing's College London · GBBirmingham Children's Hospital · GBLurie Children's Hospital · USUniversity of Manchester · GBBirmingham Women’s and Children’s NHS Foundation Trust · GBBoston Children's Hospital · USNHS Blood and Transplant · GBUniversity of Rochester Medical Center · USRoyal Children's Hospital · AUUniversity College Dublin · IECardiff University · GBManchester Academic Health Science Centre · GBRadboud University Nijmegen · NLThe University of Melbourne · AUUniversity of Washington · USRoyal Manchester Children's Hospital · GBUniversity of Tübingen · DE
Funding
A Genomic Approach to EpilepsyR01NS069605 · NINDS · UNIVERSITY OF WASHINGTON · PI MEFFORD, HEATHER C. · 2010 to 2019
$4.9MAn epigenomic approach to identifying noncoding mutations in epilepsyR00NS089858 · NINDS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CARVILL, GEMMA LOUISE · 2016 to 2018
$744kBritish Heart Foundation CH/09/003/26631British Heart Foundation RG/10/17/28553Department of Health RP-2016-07-019Medical Research Council MR/L010305/1NINDS NIH HHS R00 NS089858NINDS NIH HHS R01 NS069605Wellcome Trust
Abstract
The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Ca
Indexed as
MutationSynaptic TransmissionAdolescentCalciumCalcium Channels, N-TypeChildChild, PreschoolDyskinesiasEpilepsyFemaleHumansInfantLoss of HeterozygosityMalePedigreeCACNA1B protein, humanCalciumCalcium Channels, N-TypeCACNA1Bdevelopmental and epileptic encephalopathy (DEE)epilepsyepilepsy-dyskinesia
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