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

2.50
Hdl Handle:
http://hdl.handle.net/11287/620117
Title:
Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.
Authors:
Meyer, E.; Carss, K. J.; Rankin, Julia; Nichols, J. M. E.; Grozeva, D.; Joseph, A. P.; Mencacci, N. E.; Papandreou, A.; Ng, J.; Barral, S.; Ngoh, A.; Ben-Pazi, H.; Willemsen, M. A.; Arkadir, D.; Barnicoat, A.; Bergman, H.; Bhate, S.; Boys, A.; Darin, N.; Foulds, N.; Gutowski, Nicholas J.; Hills, A.; Houlden, H.; Hurst, J. A.; Israel, Z.; Kaminska, M.; Limousin, P.; Lumsden, D.; McKee, S. A.; Misra, S.; Mohammed, S. S.; Nakou, V.; Nicolai, J.; Nilsson, M.; Pall, H.; Peall, K. J.; Peters, G. B.; Prabhakar, P.; Reuter, M. S.; Rump, P.; Segel, R.; Sinnema, M.; Smith, M.; Turnpenny, Peter D.; White, S. M.; Wieczorek, D.; Wiethoff, S.; Wilson, B. T.; Winter, G.; Wragg, C.; Pope, S.; Heales, S. J. H.; Morrogh, D.; Pittman, A.; Carr, L. J.; Perez-Dueñas, B.; Lin, J-P; Reis, A.; Gahl, W. A.; Toro, C.; Bhatia, K. P.; Wood, N. W.; Kamsteeg, E-J; Chong, W. K.; Gissen, P.; Topf, M.; Dale, R. C.; Chubb, J.R.; Raymond, F. L.; Kurian, M. A.
Abstract:
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.
Citation:
Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia. 2017 Feb;49(2):223-237. Nat. Genet.
Publisher:
Nature
Journal:
Nature Genetics
Issue Date:
19-Dec-2016
URI:
http://hdl.handle.net/11287/620117
DOI:
10.1038/ng.3740
PubMed ID:
27992417
Additional Links:
http://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3740.html?WT.feed_name=subjects_genetics
Type:
Journal Article
Language:
en
ISSN:
1546-1718
Appears in Collections:
Neurology; Clinical Genetics (Peninsula Genetics); 2016 RD&E publications

Full metadata record

DC FieldValue Language
dc.contributor.authorMeyer, E.en
dc.contributor.authorCarss, K. J.en
dc.contributor.authorRankin, Juliaen
dc.contributor.authorNichols, J. M. E.en
dc.contributor.authorGrozeva, D.en
dc.contributor.authorJoseph, A. P.en
dc.contributor.authorMencacci, N. E.en
dc.contributor.authorPapandreou, A.en
dc.contributor.authorNg, J.en
dc.contributor.authorBarral, S.en
dc.contributor.authorNgoh, A.en
dc.contributor.authorBen-Pazi, H.en
dc.contributor.authorWillemsen, M. A.en
dc.contributor.authorArkadir, D.en
dc.contributor.authorBarnicoat, A.en
dc.contributor.authorBergman, H.en
dc.contributor.authorBhate, S.en
dc.contributor.authorBoys, A.en
dc.contributor.authorDarin, N.en
dc.contributor.authorFoulds, N.en
dc.contributor.authorGutowski, Nicholas J.en
dc.contributor.authorHills, A.en
dc.contributor.authorHoulden, H.en
dc.contributor.authorHurst, J. A.en
dc.contributor.authorIsrael, Z.en
dc.contributor.authorKaminska, M.en
dc.contributor.authorLimousin, P.en
dc.contributor.authorLumsden, D.en
dc.contributor.authorMcKee, S. A.en
dc.contributor.authorMisra, S.en
dc.contributor.authorMohammed, S. S.en
dc.contributor.authorNakou, V.en
dc.contributor.authorNicolai, J.en
dc.contributor.authorNilsson, M.en
dc.contributor.authorPall, H.en
dc.contributor.authorPeall, K. J.en
dc.contributor.authorPeters, G. B.en
dc.contributor.authorPrabhakar, P.en
dc.contributor.authorReuter, M. S.en
dc.contributor.authorRump, P.en
dc.contributor.authorSegel, R.en
dc.contributor.authorSinnema, M.en
dc.contributor.authorSmith, M.en
dc.contributor.authorTurnpenny, Peter D.en
dc.contributor.authorWhite, S. M.en
dc.contributor.authorWieczorek, D.en
dc.contributor.authorWiethoff, S.en
dc.contributor.authorWilson, B. T.en
dc.contributor.authorWinter, G.en
dc.contributor.authorWragg, C.en
dc.contributor.authorPope, S.en
dc.contributor.authorHeales, S. J. H.en
dc.contributor.authorMorrogh, D.en
dc.contributor.authorPittman, A.en
dc.contributor.authorCarr, L. J.en
dc.contributor.authorPerez-Dueñas, B.en
dc.contributor.authorLin, J-Pen
dc.contributor.authorReis, A.en
dc.contributor.authorGahl, W. A.en
dc.contributor.authorToro, C.en
dc.contributor.authorBhatia, K. P.en
dc.contributor.authorWood, N. W.en
dc.contributor.authorKamsteeg, E-Jen
dc.contributor.authorChong, W. K.en
dc.contributor.authorGissen, P.en
dc.contributor.authorTopf, M.en
dc.contributor.authorDale, R. C.en
dc.contributor.authorChubb, J.R.en
dc.contributor.authorRaymond, F. L.en
dc.contributor.authorKurian, M. A.en
dc.date.accessioned2016-12-21T10:03:28Z-
dc.date.available2016-12-21T10:03:28Z-
dc.date.issued2016-12-19-
dc.identifier.citationMutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia. 2017 Feb;49(2):223-237. Nat. Genet.en
dc.identifier.issn1546-1718-
dc.identifier.pmid27992417-
dc.identifier.doi10.1038/ng.3740-
dc.identifier.urihttp://hdl.handle.net/11287/620117-
dc.description.abstractHistone 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.en
dc.language.isoenen
dc.publisherNatureen
dc.relation.urlhttp://www.nature.com/ng/journal/vaop/ncurrent/full/ng.3740.html?WT.feed_name=subjects_geneticsen
dc.rightsArchived with thanks to Nature Geneticsen
dc.subjectWessex Classification Subject Headings::Oncology. Pathology.::Geneticsen
dc.subjectWessex Classification Subject Headings::Neurologyen
dc.titleMutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.en
dc.typeJournal Articleen
dc.identifier.journalNature Geneticsen
dc.type.versionIn press (epub ahead of print)en

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