title: Update on the Genetics of Dystonia.
abstract: Mainly due to the advent of next-generation sequencing (NGS), the field of genetics of dystonia has rapidly grown in recent years, which led to the discovery of a number of novel dystonia genes and the development of a new classification and nomenclature for inherited dystonias. In addition, new findings from both in vivo and in vitro studies have been published on the role of previously known dystonia genes, extending our understanding of the pathophysiology of dystonia. We here review the current knowledge and recent findings in the known genes for isolated dystonia TOR1A, THAP1, and GNAL as well as for the combined dystonias due to mutations in GCH1, ATP1A3, and SGCE. We present confirmatory evidence for a role of dystonia genes that had not yet been unequivocally established including PRKRA, TUBB4A, ANO3, and TAF1. We finally discuss selected novel genes for dystonia such as KMT2B and VAC14 along with the challenges for gene identification in the NGS era and the translational importance of dystonia genetics in clinical practice.
authors.affiliation: Institute of Neurogenetics, University of Luebeck, Maria-Goeppert-Str. 1, 23562, Luebeck, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Lohmann
authors.affiliation: Institute of Neurogenetics, University of Luebeck, Maria-Goeppert-Str. 1, 23562, Luebeck, Germany. christine.klein@neuro.uni-luebeck.de.
authors.forename: Christine
authors.initials: C
authors.lastname: Klein
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004421:Dystonia / Q000235:genetics* / Q000503:physiopathology; D020821:Dystonic Disorders / Q000235:genetics* / Q000503:physiopathology; D044385:GTP-Binding Protein alpha Subunits / Q000235:genetics; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D004268:DNA-Binding Proteins; D044385:GTP-Binding Protein alpha Subunits; D018832:Molecular Chaperones; D009687:Nuclear Proteins; C474080:THAP1 protein, human; C108175:TOR1A protein, human; C084618:olfactory G protein subunit alpha olf
keywords: Classification; Dystonia; Mutation; Next-generation sequencing; Nomenclature; Novel genes