Your browser doesn't support javascript.
loading
Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.
Meyer, Esther; Carss, Keren J; Rankin, Julia; Nichols, John M E; Grozeva, Detelina; Joseph, Agnel P; Mencacci, Niccolo E; Papandreou, Apostolos; Ng, Joanne; Barral, Serena; Ngoh, Adeline; Ben-Pazi, Hilla; Willemsen, Michel A; Arkadir, David; Barnicoat, Angela; Bergman, Hagai; Bhate, Sanjay; Boys, Amber; Darin, Niklas; Foulds, Nicola; Gutowski, Nicholas; Hills, Alison; Houlden, Henry; Hurst, Jane A; Israel, Zvi; Kaminska, Margaret; Limousin, Patricia; Lumsden, Daniel; McKee, Shane; Misra, Shibalik; Mohammed, Shekeeb S; Nakou, Vasiliki; Nicolai, Joost; Nilsson, Magnus; Pall, Hardev; Peall, Kathryn J; Peters, Gregory B; Prabhakar, Prab; Reuter, Miriam S; Rump, Patrick; Segel, Reeval; Sinnema, Margje; Smith, Martin; Turnpenny, Peter; White, Susan M; Wieczorek, Dagmar; Wiethoff, Sarah; Wilson, Brian T; Winter, Gidon; Wragg, Christopher.
Afiliação
  • Meyer E; Molecular Neurosciences, Developmental Neurosciences, UCL Institute of Child Health, London, UK.
  • Carss KJ; Department of Hematology, University of Cambridge, NHS Blood and Transplant Centre, Cambridge, UK.
  • Rankin J; NIHR BioResource-Rare Diseases, Cambridge University Hospitals, Cambridge Biomedical Campus, Cambridge, UK.
  • Nichols JM; Clinical Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • Grozeva D; MRC Laboratory for Molecular Cell Biology and Department of Cell and Developmental Biology, University College London, London, UK.
  • Joseph AP; Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
  • Mencacci NE; Institute of Structural and Molecular Biology, Crystallography/Department of Biological Sciences, Birkbeck College, University of London, London, UK.
  • Papandreou A; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
  • Ng J; Molecular Neurosciences, Developmental Neurosciences, UCL Institute of Child Health, London, UK.
  • Barral S; Department of Neurology, Great Ormond Street Hospital, London, UK.
  • Ngoh A; Molecular Neurosciences, Developmental Neurosciences, UCL Institute of Child Health, London, UK.
  • Ben-Pazi H; Department of Neurology, Great Ormond Street Hospital, London, UK.
  • Willemsen MA; Molecular Neurosciences, Developmental Neurosciences, UCL Institute of Child Health, London, UK.
  • Arkadir D; Molecular Neurosciences, Developmental Neurosciences, UCL Institute of Child Health, London, UK.
  • Barnicoat A; Department of Neurology, Great Ormond Street Hospital, London, UK.
  • Bergman H; Pediatric Neurology and Development, Shaare-Zedek Hospital, Jerusalem, Israel.
  • Bhate S; Department of Paediatric Neurology, Donders Centre for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Boys A; Department of Neurology, Hadassah Medical Center and Hebrew University, Jerusalem, Israel.
  • Darin N; Department of Clinical Genetics, Great Ormond Street Hospital, London, UK.
  • Foulds N; Department of Neurobiology and Neurosurgery, Hebrew University, Hadassah Medical Centre, Jerusalem, Israel.
  • Gutowski N; Department of Neurology, Great Ormond Street Hospital, London, UK.
  • Hills A; Victoria Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Victoria, Australia.
  • Houlden H; Department of Pediatrics, Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
  • Hurst JA; Department of Clinical Genetics, Southampton General Hospital, Southampton, UK.
  • Israel Z; Department of Neurology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
  • Kaminska M; Bristol Genetics Laboratory, Pathology Sciences, Southmead Hospital, Bristol, UK.
  • Limousin P; Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
  • Lumsden D; Department of Clinical Genetics, Great Ormond Street Hospital, London, UK.
  • McKee S; Functional and Restorative Neurosurgery, Hadassah University Hospital, Jerusalem, Israel.
  • Misra S; Complex Motor Disorders Service, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
  • Mohammed SS; Sobell Department, National Hospital for Neurology and Neurosurgery, London, UK.
  • Nakou V; Complex Motor Disorders Service, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
  • Nicolai J; Northern Ireland Regional Genetics Service, Belfast City Hospital, Belfast, UK.
  • Nilsson M; Child and Adolescent Health, University of Sydney, Sydney, New South Wales, Australia.
  • Pall H; Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, University of Sydney, Sydney, New South Wales, Australia.
  • Peall KJ; Child and Adolescent Health, University of Sydney, Sydney, New South Wales, Australia.
  • Peters GB; Institute for Neuroscience and Muscle Research, Children's Hospital at Westmead, University of Sydney, Sydney, New South Wales, Australia.
  • Prabhakar P; Complex Motor Disorders Service, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
  • Reuter MS; Department of Neurology, Maastricht University Medical Center, Maastricht, the Netherlands.
  • Rump P; Department of Pediatrics, Piteå Hospital and Umeå University Hospital, Umeå, Sweden.
  • Segel R; College of Medicine and Dental Studies, University of Birmingham, Birmingham, UK.
  • Sinnema M; Neuroscience and Mental Health Research Institute, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
  • Smith M; Department of Cytogenetics, Children's Hospital at Westmead, Westmead, New South Wales, Australia.
  • Turnpenny P; Department of Neurology, Great Ormond Street Hospital, London, UK.
  • White SM; Institute of Human Genetics, Friedrich Alexander Universität Erlangen-Nürnberg, Erlangen, Germany.
  • Wieczorek D; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
  • Wiethoff S; Medical Genetics Institute and Pediatrics, Shaare-Zedek Medical Center and Hebrew University School of Medicine, Jerusalem, Israel.
  • Wilson BT; Department of Clinical Genetics and School for Oncology and Developmental Biology (GROW), Maastricht University Medical Center, Maastricht, the Netherlands.
  • Winter G; Department of Pediatric Neurology, John Radcliffe Hospital, Oxford, UK.
  • Wragg C; Clinical Genetics, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.
Nat Genet ; 49(2): 223-237, 2017 Feb.
Article em En | MEDLINE | ID: mdl-27992417
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.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Histona-Lisina N-Metiltransferase / Distonia / Mutação Limite: Adolescent / Female / Humans / Male Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Histona-Lisina N-Metiltransferase / Distonia / Mutação Limite: Adolescent / Female / Humans / Male Idioma: En Revista: Nat Genet Assunto da revista: GENETICA MEDICA Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Reino Unido