Journal
NATURE GENETICS
Volume 49, Issue 2, Pages 223-237Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3740
Keywords
-
Categories
Funding
- Rosetrees Trust
- Great Ormond Street Hospital Children's Charity
- Gracious Heart Foundation
- UK Department of Health's NIHR Biomedical Research Centers
- Daniel Turnberg Trust Fund
- MRC
- Wellcome Trust (Synaptopathies award)
- Prusiner-Abramsky Award
- Dystonia Society (UK)
- La Marato de TV3 [20143130]
- Ministerio Espanol de Economia y Competitividad [PI15/00287]
- Guy's and St Thomas' Charity New Services and Innovation Grant [G060708]
- Dystonia Society (UK) [01/2011, 07/2013]
- Action Medical Research [AMR-GN2097]
- NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust
- University College London
- University of Cambridge
- NIHR for the BioResource for Rare Diseases [RG65966]
- Wellcome Trust [UK10K (WT091310)]
- DDD study
- Health Innovation Challenge Fund [HICF-1009-003]
- Intramural Research Program of the National Human Genome Research Institute
- Common Fund, NIH Office of the Director
- German Ministry of Research and Education as part of National Genome Research Network [0IGS08160, 01GS08167]
- German Ministry of Research and Education (German Mental Retardation Network) as part of National Genome Research Network
- Deutsche Forschungsgemeinschaft [AB393/2-2]
- UK Human Brain Expression Consortium (UKBEC)
- MRC [MR/K02342X/1, G108/638, G1001253, MR/J004758/1, G0802760, MR/P008593/1] Funding Source: UKRI
- Academy of Medical Sciences (AMS) [AMS-SGCL11-Peall] Funding Source: researchfish
- Action Medical Research [2465, 2358] Funding Source: researchfish
- Great Ormond Street Hospital Childrens Charity [V1284] Funding Source: researchfish
- Medical Research Council [G1001253, MR/K02342X/1, MR/J004758/1, MR/P008593/1, G108/638, G0802760] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0513-10064, NF-SI-0515-10082, NF-SI-0507-10376] Funding Source: researchfish
- Parkinson's UK [G-1107] Funding Source: researchfish
- Rosetrees Trust [M576] Funding Source: researchfish
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available