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Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia
- Source :
- Nature Genetics, 49, 223-237, Nature Genetics, 49(2), 223-237. Nature Publishing Group, Nature Genetics, 49, 2, pp. 223-237
- Publication Year :
- 2017
-
Abstract
- Item does not contain fulltext 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.
- Subjects :
- 0301 basic medicine
Male
Methyltransferase
Deep brain stimulation
Adolescent
Histone lysine methylation
DISORDERS
medicine.medical_treatment
VARIANTS
Bioinformatics
bcs
Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]
MECHANISMS
Histones
03 medical and health sciences
BRAIN IRON ACCUMULATION
Genetics
medicine
KABUKI SYNDROME
Humans
Laryngeal dystonia
Dystonia
Regulation of gene expression
biology
Lysine
METHYLATION
NEURODEGENERATION
Nuclear Proteins
Histone-Lysine N-Methyltransferase
medicine.disease
Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3]
DNA-Binding Proteins
030104 developmental biology
Histone
Histone methyltransferase
Mathematik
Mutation
biology.protein
Histone Methyltransferases
UPDATE
Female
PROTEIN STABILITY
LEUKEMIA
Subjects
Details
- ISSN :
- 10614036
- Database :
- OpenAIRE
- Journal :
- Nature Genetics, 49, 223-237, Nature Genetics, 49(2), 223-237. Nature Publishing Group, Nature Genetics, 49, 2, pp. 223-237
- Accession number :
- edsair.doi.dedup.....57c4afa1a02017040dfcd473edd7a70e