{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:08:24Z","timestamp":1792084104075,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T00:00:00Z","timestamp":1705017600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01GM1514B"],"award-info":[{"award-number":["01GM1514B"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["LO1555\/10\u20101"],"award-info":[{"award-number":["LO1555\/10\u20101"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Pathogenic variants in several genes have been linked to genetic forms of isolated or combined dystonia. The phenotypic and genetic spectrum and the frequency of pathogenic variants in these genes have not yet been fully elucidated, neither in patients with dystonia nor with other, sometimes co\u2010occurring movement disorders such as Parkinson's disease (PD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To screen &gt;2000 patients with dystonia or PD for rare variants in known dystonia\u2010causing genes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We screened 1207 dystonia patients from Germany (DysTract consortium), Spain, and South Korea, and 1036 PD patients from Germany for pathogenic variants using a next\u2010generation sequencing gene panel. The impact on DNA methylation of <jats:italic>KMT2B<\/jats:italic> variants was evaluated by analyzing the gene's characteristic episignature.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 171 carriers (109 with dystonia [9.0%]; 62 with PD [6.0%]) of 131 rare variants (minor allele frequency &lt;0.005). A total of 52 patients (48 dystonia [4.0%]; four PD [0.4%, all with <jats:italic>GCH1<\/jats:italic> variants]) carried 33 different (likely) pathogenic variants, of which 17 were not previously reported. Pathogenic biallelic variants in <jats:italic>PRKRA<\/jats:italic> were not found. Episignature analysis of 48 <jats:italic>KMT2B<\/jats:italic> variants revealed that only two of these should be considered (likely) pathogenic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study confirms pathogenic variants in <jats:italic>GCH1<\/jats:italic>, <jats:italic>GNAL<\/jats:italic>, <jats:italic>KMT2B<\/jats:italic>, <jats:italic>SGCE<\/jats:italic>, <jats:italic>THAP1<\/jats:italic>, and <jats:italic>TOR1A<\/jats:italic> as relevant causes in dystonia and expands the mutational spectrum. Of note, likely pathogenic variants only in <jats:italic>GCH1<\/jats:italic> were also found among PD patients. For DYT\u2010KMT2B, the recently described episignature served as a reliable readout to determine the functional effect of newly identified variants. \u00a9 2024 The Authors. <jats:italic>Movement Disorders<\/jats:italic> published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29693","type":"journal-article","created":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T04:49:21Z","timestamp":1705034961000},"page":"526-538","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Large\u2010Scale Screening: Phenotypic and Mutational Spectrum in Isolated and Combined Dystonia Genes"],"prefix":"10.1002","volume":"39","author":[{"given":"Mirja","family":"Thomsen","sequence":"first","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck 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