Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia

Journal article

Publication Details

Author(s): Meyer E, Carss KJ, Rankin J, Nichols JME, Grozeva D, Joseph AP, Mencacci NE, Papandreou A, Ng J, Barra S, Ngoh A, Ben-Pazi H, Willemsen MA, Arkadir D, Barnicoat A, Bergman H, Bhate S, Boys A, Darin N, Foulds N, Gutowski N, Hills A, Houlden H, Hurst JA, Israe Z, Kaminska M, Limousin P, Lumsden D, Mckee S, Misra S, Mohammed SS, Nakou V, Nicolai J, Nilsson M, Pall H, Peall KJ, Peters GB, Prabhakar P, Reuter M, Rump P, Sege R, Sinnema M, Smith M, Turnpenny P, White SM, Wieczorek D, Wiethoff S, Wilson BT, Winter G, Wragg C, Pope S, Heales SJH, Morrogh D, Pittman A, Carr LJ, Perez-Duenas B, Lin JP, Reis A, Gahl WA, Toro C, Bhatia KP, Wood NW, Kamsteeg EJ, Chong WK, Gissen P, Topf M, Dale RC, Chubby JR, Raymond FL, Kurian MA
Journal: Nature Genetics
Publication year: 2016
ISSN: 1061-4036


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.

FAU Authors / FAU Editors

Reuter, Miriam Dr. med.
Humangenetisches Institut

External institutions with authors

Belfast City Hospital / Ospidéal Chathair Bhéal Feirste
Cambridge University Hospital
Cardiff University
Great Ormond Street Hospital (GOSH)
Guy's and St Thomas'
Hadassah Medical Center / מרכז רפואי הדסה‎‎
Hebrew University of Jerusalem
John Radcliffe Hospital
Maastricht University
Murdoch Childrens Research Institute
Piteå hospital och asyl
Radboud University Nijmegen
Radboud University Nijmegen Medical Centre / Radboudumc of voluit Radboud Universitair Medisch Centrum (UMC)
Royal Devon & Exeter NHS Foundation Trust
Shaare Zedek Medical Center / מרכז רפואי שערי צדק‎‎,
Southmead Hospital
Universitat de Barcelona (UB) / University of Barcelona
Universität Duisburg-Essen (UDE)
University College London Hospitals (UCLH)
University College London (UCL)
University Hospital Southampton NHS
University of Birmingham
University of Cambridge
University of Gothenburg / Göteborgs universitet
University of Groningen / Rijksuniversiteit Groningen
University of Sydney
US National Institutes of Health (NIH)
Westmead Hospital

How to cite

Meyer, E., Carss, K.J., Rankin, J., Nichols, J.M.E., Grozeva, D., Joseph, A.P.,... Kurian, M.A. (2016). Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia. Nature Genetics.

Meyer, Esther, et al. "Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia." Nature Genetics (2016).


Last updated on 2019-13-01 at 07:08