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

Authors :
Brian T. Wilson
Vasiliki Nakou
Henry Houlden
Angela Barnicoat
Joost Nicolai
Miriam S. Reuter
Patrick Rump
F Lucy Raymond
Nicholas W. Wood
Serena Barral
Sanjay Bhate
Jonathan R. Chubb
Manju A. Kurian
Michèl A.A.P. Willemsen
Esther Meyer
André Reis
Nicola Foulds
Shekeeb S Mohammed
Kathryn J. Peall
Patricia Limousin
Apostolos Papandreou
Margaret Kaminska
Magnus Nilsson
Russell C. Dale
Susan M. White
Paul Gissen
Hilla Ben-Pazi
Gregory Peters
Christopher Wragg
Zvi Israel
Jean-Pierre Lin
Sarah Wiethoff
Simon Pope
Deciphering Developmental Disorders Study
William A. Gahl
Alan Pittman
Niccolo E. Mencacci
Wui K. Chong
Margje Sinnema
Dagmar Wieczorek
Erik-Jan Kamsteeg
Martin Smith
A. Hills
John M.E. Nichols
Shane McKee
Keren J. Carss
Maya Topf
S Heales
Gidon Winter
Amber Boys
Hardev Pall
Peter D. Turnpenny
Camilo Toro
Julia Rankin
Jane A. Hurst
Reeval Segel
Nicholas Gutowski
Hagai Bergman
Niklas Darin
Shibalik Misra
Lucinda Carr
Agnel Praveen Joseph
Joanne Ng
Deborah Morrogh
David Arkadir
Detelina Grozeva
Adeline Ngoh
Daniel E. Lumsden
Belén Pérez-Dueñas
Prab Prabhakar
Kailash P. Bhatia
Klinische Neurowetenschappen
MUMC+: MA Med Staf Spec Neurologie (9)
MUMC+: DA KG Polikliniek (9)
RS: FHML non-thematic output
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.

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