Publication year
2017Author(s)
Source
Nature Genetics, 49, 2, (2017), pp. 223-237ISSN
Publication type
Article / Letter to editor

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Organization
Paediatrics
Paediatrics - OUD tm 2017
Neurology
Radboudumc Extern
Human Genetics
Journal title
Nature Genetics
Volume
vol. 49
Issue
iss. 2
Page start
p. 223
Page end
p. 237
Subject
Radboudumc 12: Sensory disorders DCMN: Donders Center for Medical Neuroscience; Radboudumc 3: Disorders of movement DCMN: Donders Center for Medical NeuroscienceAbstract
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.
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- Academic publications [227437]
- Faculty of Medical Sciences [86157]
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