{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:26:55Z","timestamp":1790299615931,"version":"4.1.0"},"reference-count":9,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T00:00:00Z","timestamp":1732147200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Population\u2010scale databases majorly contribute to variant interpretation. The recently released Genome Aggregation Database (gnomAD) v4 offers a &gt;5\u2010fold increased sample size compared to v2.1.1. Pathogenic variants absent from v2.1.1 are now registered in v4 at a considerable rate. The implications on variant interpretation in dystonia are unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>All curated variants linked to the most common dominant forms of isolated dystonia were extracted from the International Parkinson's Disease and Movement Disorder Society Gene database. We compared variant population\u2010frequencies and gene constraint metrics between gnomAD v2.1.1 and v4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The majority of dystonia\u2010causing variants (192\/247, 77.7%) remained absent from the newer gnomAD version. Of 219 variants absent from v2.1.1, 27 (12.3%) appeared for the first time in v4.1, including well\u2010established pathogenic alleles. Gene constraints for <jats:italic>GNAL<\/jats:italic> and <jats:italic>KMT2B<\/jats:italic> significantly decreased in v4.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>A growing number of dystonia\u2010linked alleles are seen in gnomAD v4. The presence in population\u2010scale data does not preclude pathogenicity. \u00a9 2024 The Author(s). <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.30066","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T07:45:56Z","timestamp":1732175156000},"page":"357-362","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genome Aggregation Database Version 4\u2014Allele Frequency Changes and Impact on Variant Interpretation in Dystonia"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0217-8630","authenticated-orcid":false,"given":"Elisabetta","family":"Indelicato","sequence":"first","affiliation":[{"name":"Center for Rare Movement Disorders Innsbruck, Department of Neurology Medical University Innsbruck  Innsbruck Austria"},{"name":"Institute of Neurogenomics, Helmholtz Munich  Neuherberg Germany"},{"name":"Institute of Human Genetics Technical University of Munich, School of Medicine and Health  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Eberl","sequence":"additional","affiliation":[{"name":"Center for Rare Movement Disorders Innsbruck, Department of Neurology Medical University Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Boesch","sequence":"additional","affiliation":[{"name":"Center for Rare Movement Disorders Innsbruck, Department of Neurology Medical University Innsbruck  Innsbruck Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara M.","family":"Lange","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Department of Neurology University Hospital Schleswig\u2010Holstein  Luebeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Klein","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"},{"name":"Department of Neurology University Hospital Schleswig\u2010Holstein  Luebeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5121-1460","authenticated-orcid":false,"given":"Katja","family":"Lohmann","sequence":"additional","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck  L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8112-9153","authenticated-orcid":false,"given":"Michael","family":"Zech","sequence":"additional","affiliation":[{"name":"Institute of Neurogenomics, Helmholtz Munich  Neuherberg Germany"},{"name":"Institute of Human Genetics Technical University of Munich, School of Medicine and Health  Munich Germany"},{"name":"Institute for Advanced Study Technical University of Munich  Garching Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28982"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29797"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28485"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000358"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1661343"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab360"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27026"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.30066","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T11:30:49Z","timestamp":1760959849000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.30066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,21]]},"references-count":9,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,2]]}},"alternative-id":["10.1002\/mds.30066"],"URL":"https:\/\/doi.org\/10.1002\/mds.30066","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,21]]},"assertion":[{"value":"2024-07-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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