{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T12:06:53Z","timestamp":1789214813684,"version":"build-2803163510"},"reference-count":14,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T00:00:00Z","timestamp":1495065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:bold>Background<\/jats:bold>: Recently a novel syndrome of childhood\u2010onset generalized dystonia originating from mutations in lysine\u2010specific methyltransferase 2B (<jats:italic>KMT2B<\/jats:italic>) has been reported.<\/jats:p><jats:p><jats:bold>Methods<\/jats:bold>: We sequenced the exomes of 4 generalized dystonia\u2010affected probands recruited from a Prague movement disorders center (Czech Republic). Bioinformatics analyses were conducted to select candidate causal variants in described dystonia\u2010mutated genes. After cosegregation testing, checklists from the American College of Medical Genetics and Genomics were adopted to judge variant pathogenicity.<\/jats:p><jats:p><jats:bold>Results<\/jats:bold>: Three novel, predicted protein\u2010damaging missense variants in <jats:italic>KMT2B<\/jats:italic> were identified (p.Glu1234Lys, p.Ala1541Val, p.Arg1779Gln). Meeting pathogenicity criteria, p.Glu1234Lys was absent from population\u2010based controls, situated in a key protein domain, and had occurred de novo. The associated phenotype comprised adolescence\u2010onset generalized isolated dystonia with prominent speech impairment. Although linked to a similar clinical expression, p.Ala1541Val and p.Arg1779Gln remained of uncertain significance.<\/jats:p><jats:p><jats:bold>Conclusions<\/jats:bold>: Rare missense variation in <jats:italic>KMT2B<\/jats:italic> represents an additional cause of generalized dystonia. Application of sequence interpretation standards is required before assigning pathogenicity to a <jats:italic>KMT2B<\/jats:italic> missense variant. \u00a9 2017 International Parkinson and Movement Disorder Society<\/jats:p>","DOI":"10.1002\/mds.27026","type":"journal-article","created":{"date-parts":[[2017,5,18]],"date-time":"2017-05-18T08:50:16Z","timestamp":1495097416000},"page":"1087-1091","source":"Crossref","is-referenced-by-count":45,"title":["<i>KMT2B<\/i> rare missense variants in generalized dystonia"],"prefix":"10.1002","volume":"32","author":[{"given":"Michael","family":"Zech","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Neurogenomik, Helmholtz Zentrum M\u00fcnchen Munich Germany"},{"name":"Klinik und Poliklinik f\u00fcr Neurologie Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Jech","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience First Faculty of Medicine, Charles University and General Faculty Hospital Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Havr\u00e1nkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience First Faculty of Medicine, Charles University and General Faculty Hospital Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Fe\u010d\u00edkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience First Faculty of Medicine, Charles University and General Faculty Hospital Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Berutti","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik, Helmholtz Zentrum M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du\u0161an","family":"Urgo\u0161\u00edk","sequence":"additional","affiliation":[{"name":"Department of Stereotactic Neurosurgery and Radiosurgery Na Homolce Hospital Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Kemlink","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience First Faculty of Medicine, Charles University and General Faculty Hospital Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim M.","family":"Strom","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Humangenetik, Helmholtz Zentrum M\u00fcnchen Munich Germany"},{"name":"Institut f\u00fcr Humangenetik, Technische Universit\u00e4t M\u00fcnchen Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Roth","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience First Faculty of Medicine, Charles University and General Faculty Hospital Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ev\u017een","family":"R\u016f\u017ei\u010dka","sequence":"additional","affiliation":[{"name":"Department of Neurology and Center of Clinical Neuroscience First Faculty of Medicine, Charles University and General Faculty Hospital Prague Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane","family":"Winkelmann","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Neurogenomik, Helmholtz Zentrum M\u00fcnchen Munich Germany"},{"name":"Klinik und Poliklinik f\u00fcr Neurologie Klinikum rechts der Isar, Technische Universit\u00e4t M\u00fcnchen Munich Germany"},{"name":"Institut f\u00fcr Humangenetik, Technische Universit\u00e4t M\u00fcnchen Munich Germany"},{"name":"Munich Cluster for Systems Neurology, SyNergy Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,5,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25475"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000114"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1353-8020(13)70033-6"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26600"},{"key":"e_1_2_8_6_1","article-title":"Clinical exome sequencing in early\u2010onset generalized dystonia and large\u2010scale resequencing follow\u2010up [published online ahead of print 2016]","author":"Zech M","journal-title":"Mov 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