ArticleNature genetics2017
Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.
Erratum issuedOpen access · greenAbstract read
In one paragraph
Article in Nature genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 115 papers, 5 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed, 5 pooled it
11.8field-weighted citation impact, top 1% of its field
What it found
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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.
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Who cites it
115 citing papers in PubMed, 5 syntheses or guidelines pooled it, 238 citations in OpenAlex.
- Decoding the Alphabet Soup: A Practical Guide to Genetic Testing in Hyperkinetic Movement Disorders.Tremor and other hyperkinetic movements (New York, N.Y.) · 2025Pooled it
- Identification of a novel de novo KMT2B variant in a Greek dystonia patient via exome sequencing genotype-phenotype correlations of all published cases.Molecular biology reports · 2021Pooled it
- Deep brain stimulation in pediatric dystonia: a systematic review.Neurosurgical review · 2020Pooled it
- Predictive factors of outcome in cervical dystonia following deep brain stimulation: an individual patient data meta-analysis.Journal of neurology · 2020Pooled it
- Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neuroendocrine Tumors (ROHHADNET) Syndrome: A Systematic Review.BioMed research international · 2018Pooled it
- Nanopore long-read sequencing facilitates accurate diagnosis of KMT2B-related dystonia.Clinical epigenetics · 2026Article
- Genetic analysis of childhood-onset dystonia-28 caused by a variant (c.5076G>A) in theGlobal medical genetics · 2026Article
- Clinical, imaging and genetic profile of KMT2B-related dystonia: a review of published cases.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Rare protein-coding variation and the genetic architecture of height in >1.4 million individuals.medRxiv : the preprint server for health sciences · 2026Article
- Bilateral pallidotomy for DYT-28 generalized primary dystonia in a child: a case report and review of literature.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2026Review
- Developmental, Neuroanatomical and Cellular Expression of Genes Causing Dystonia.Annals of clinical and translational neurology · 2026Article
- Review
- Nap1L4a Cooperates with Scl/Klf1 to Recruit H2A.Z in Mediating Interactions Among Cis-Regulatory Elements and Transcription Required for Primitive Erythropoiesis in Zebrafish.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dystonia: Insights into Mechanisms and Novel Therapeutics.Current neurology and neuroscience reports · 2026Review
- Clinical immunology in chromatinopathies: a scoping review.Frontiers in immunology · 2026Article
- Novel heterozygous mutation in KMT2B causing an unusual phenotypic presentation: a comprehensive clinical and bioinformatic analysis.Molecular biology reports · 2025Article
- Combined genomics and proteomics unveils elusive variants and vast aetiologic heterogeneity in dystonia.Brain : a journal of neurology · 2025Article
- Spiking Patterns in the Globus Pallidus Highlight Convergent Neural Dynamics across Diverse Genetic Dystonia Syndromes.Annals of neurology · 2025Article
- Molecular and clinical aspects of histone-related disorders.Human genomics · 2025Review
- Insights on the Shared Genetic Landscape of Neurodevelopmental and Movement Disorders.Current neurology and neuroscience reports · 2025Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
- Erratum issued
Authors and funding
73 authors at 20 institutions in 8 countries.
Esther MeyerMolecular Neurosciences, Developmental Neurosciences, UCL Institute of Child Health, London, UK.
Keren J CarssDepartment of Hematology, University of Cambridge, NHS Blood and Transplant Centre, Cambridge, UK.
Julia RankinClinical Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
John M E NicholsMRC Laboratory for Molecular Cell Biology and Department of Cell and Developmental Biology, University College London, London, UK.
Detelina GrozevaDepartment of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Agnel P JosephInstitute of Structural and Molecular Biology, Crystallography/Department of Biological Sciences, Birkbeck College, University of London, London, UK.
Niccolo E MencacciDepartment of Molecular Neuroscience, UCL Institute of Neurology, London, UK.ORCID http://orcid.org/0000-0003-3383-9665
Apostolos PapandreouMolecular Neurosciences, Developmental Neurosciences, UCL Institute of Child Health, London, UK.ORCID http://orcid.org/0000-0001-5093-6075
Joanne NgMolecular Neurosciences, Developmental Neurosciences, UCL Institute of Child Health, London, UK.
Serena BarralMolecular Neurosciences, Developmental Neurosciences, UCL Institute of Child Health, London, UK.
Adeline NgohMolecular Neurosciences, Developmental Neurosciences, UCL Institute of Child Health, London, UK.
Hilla Ben-PaziPediatric Neurology and Development, Shaare-Zedek Hospital, Jerusalem, Israel.
Michel A WillemsenDepartment of Paediatric Neurology, Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
David ArkadirDepartment of Neurology, Hadassah Medical Center and Hebrew University, Jerusalem, Israel.
Angela BarnicoatDepartment of Clinical Genetics, Great Ormond Street Hospital, London, UK.
Hagai BergmanDepartment of Neurobiology and Neurosurgery, Hebrew University, Hadassah Medical Centre, Jerusalem, Israel.ORCID http://orcid.org/0000-0002-2402-6673
Sanjay BhateDepartment of Neurology, Great Ormond Street Hospital, London, UK.
Amber BoysVictoria Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
Niklas DarinDepartment of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
Nicola FouldsDepartment of Clinical Genetics, Southampton General Hospital, Southampton, UK.
Nicholas GutowskiDepartment of Neurology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
Alison HillsBristol Genetics Laboratory, Pathology Sciences, Southmead Hospital, Bristol, UK.
Henry HouldenDepartment of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Jane A HurstDepartment of Clinical Genetics, Great Ormond Street Hospital, London, UK.
Zvi IsraelFunctional and Restorative Neurosurgery, Hadassah University Hospital, Jerusalem, Israel.
Margaret KaminskaComplex Motor Disorders Service, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Patricia LimousinSobell Department, National Hospital for Neurology and Neurosurgery, London, UK.
Daniel LumsdenComplex Motor Disorders Service, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Shane McKeeNorthern Ireland Regional Genetics Service, Belfast City Hospital, Belfast, UK.ORCID http://orcid.org/0000-0002-1772-0106
Shibalik MisraChild and Adolescent Health, University of Sydney, Sydney, New South Wales, Australia.
Shekeeb S MohammedChild and Adolescent Health, University of Sydney, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0003-1219-4781
Vasiliki NakouComplex Motor Disorders Service, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Joost NicolaiDepartment of Neurology, Maastricht University Medical Center, Maastricht, the Netherlands.
Magnus NilssonDepartment of Pediatrics, Piteå Hospital and Umeå University Hospital, Umeå, Sweden.
Hardev PallCollege of Medicine and Dental Studies, University of Birmingham, Birmingham, UK.
Kathryn J PeallNeuroscience and Mental Health Research Institute, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Gregory B PetersDepartment of Cytogenetics, Children's Hospital at Westmead, Westmead, New South Wales, Australia.
Prab PrabhakarDepartment of Neurology, Great Ormond Street Hospital, London, UK.
Miriam S ReuterInstitute of Human Genetics, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
Patrick RumpDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.ORCID http://orcid.org/0000-0003-4059-0247
Reeval SegelMedical Genetics Institute and Pediatrics, Shaare-Zedek Medical Center and Hebrew University School of Medicine, Jerusalem, Israel.
Margje SinnemaDepartment of Clinical Genetics and School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center, Maastricht, the Netherlands.
Martin SmithDepartment of Pediatric Neurology, John Radcliffe Hospital, Oxford, UK.
Peter TurnpennyClinical Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
Susan M WhiteVictoria Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Victoria, Australia.ORCID http://orcid.org/0000-0001-7611-634X
Dagmar WieczorekInstitute of Human Genetics, University Duisburg-Essen, Essen, Germany.
Sarah WiethoffDepartment of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Brian T WilsonDepartment of Clinical Genetics, Great Ormond Street Hospital, London, UK.
Gidon WinterPediatric Neurology and Development, Shaare-Zedek Hospital, Jerusalem, Israel.
Christopher WraggBristol Genetics Laboratory, Pathology Sciences, Southmead Hospital, Bristol, UK.
Simon PopeNeurometabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK.
Simon J H HealesNeurometabolic Unit, National Hospital for Neurology and Neurosurgery, London, UK.
Deborah MorroghNorth East Thames Regional Genetics Service, Great Ormond Street Hospital, London, UK.
UK10K Consortium
Deciphering Developmental Disorders Study
NIHR BioResource Rare Diseases Consortium
Alan PittmanDepartment of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Lucinda J CarrDepartment of Neurology, Great Ormond Street Hospital, London, UK.
Belen Perez-DueñasDepartment of Child Neurology, Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona, Spain.
Jean-Pierre LinComplex Motor Disorders Service, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Andre ReisInstitute of Human Genetics, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.ORCID http://orcid.org/0000-0002-6301-6363
William A GahlNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, US National Institutes of Health, Bethesda, Maryland, USA.
Camilo ToroNIH Undiagnosed Diseases Program, Common Fund, Office of the Director, US National Institutes of Health, Bethesda, Maryland, USA.
Kailash P BhatiaSobell Department, National Hospital for Neurology and Neurosurgery, London, UK.
Nicholas W WoodDepartment of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Erik-Jan KamsteegDepartment of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands.
Wui K ChongDepartment of Radiology, Great Ormond Street Hospital, London, UK.
Paul GissenMRC Laboratory for Molecular Cell Biology and Department of Cell and Developmental Biology, University College London, London, UK.ORCID http://orcid.org/0000-0002-9712-6122
Maya TopfInstitute of Structural and Molecular Biology, Crystallography/Department of Biological Sciences, Birkbeck College, University of London, London, UK.
Russell C DaleChild and Adolescent Health, University of Sydney, Sydney, New South Wales, Australia.
Jonathan R ChubbMRC Laboratory for Molecular Cell Biology and Department of Cell and Developmental Biology, University College London, London, UK.
F Lucy RaymondNIHR BioResource-Rare Diseases, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, UK.
Manju A KurianMolecular Neurosciences, Developmental Neurosciences, UCL Institute of Child Health, London, UK.
Great Ormond Street Hospital · GBRoyal Devon & Exeter NHS Foundation Trust · GBThe University of Sydney · AUGuy's and St Thomas' NHS Foundation Trust · GBRadboud University Nijmegen · NLUniversity College London · GBUniversity of Cambridge · GBHadassah Medical Center · ILNational Institutes of Health · USSouthmead Hospital · GBFriedrich-Alexander-Universität Erlangen-Nürnberg · DEHospital Sant Joan de Déu Barcelona · ESNational Hospital for Neurology and Neurosurgery · GBNHS Blood and Transplant · GBSahlgrenska University Hospital · SEUniversity Medical Center Groningen · NLCardiff University · GBChildren's Hospital at Westmead · AUHeinrich Heine University Düsseldorf · DEJohn Radcliffe Hospital · GB
Funding
NHGRI/DIR Clinical Support ServicesZIDHG200352 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI SOLOMON, BENJAMIN · 2009 to 2025
$182.8MHuman Biochemical GeneticsZIAHG000215 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI GAHL, WILLIAM · 2009 to 2025
$72.6MMedical Research Council G0802760Medical Research Council G1001253Medical Research Council G108/638Medical Research Council MC_PC_15018Medical Research Council MR/J004758/1Medical Research Council MR/K02342X/1Medical Research Council MR/P008593/1Parkinson's UK G-1107
Abstract
Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.
Indexed as
AdolescentDNA-Binding ProteinsDystoniaFemaleHistone-Lysine N-MethyltransferaseHistone MethyltransferasesHistonesHumansLysineMaleMethylationMutationNuclear ProteinsDNA-Binding ProteinsHistone-Lysine N-MethyltransferaseHistone MethyltransferasesHistonesKMT2B protein, humanLysineNuclear Proteins
Identifiers
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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.