{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T02:54:48Z","timestamp":1787540088697,"version":"build-2736575974"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T00:00:00Z","timestamp":1762473600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1805021N"],"award-info":[{"award-number":["1805021N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FORT23\/00034,PI21\/00248,PI24\/01083"],"award-info":[{"award-number":["FORT23\/00034,PI21\/00248,PI24\/01083"]}],"id":[{"id":"10.13039\/501100004587","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":[[2026,1]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n DYT<\/jats:styled-content>\n \u2010\n \n VPS16<\/jats:italic>\n <\/jats:styled-content>\n , an early\u2010onset isolated dystonia caused by variants in the\n \n VPS16<\/jats:italic>\n <\/jats:styled-content>\n gene, has been reported in fewer than 70 patients.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We explored the clinical and genotypic spectrum of\n DYT<\/jats:styled-content>\n \u2010\n \n VPS16<\/jats:italic>\n <\/jats:styled-content>\n by investigating early\u2010onset dystonia patients with\n \n VPS16<\/jats:italic>\n <\/jats:styled-content>\n variants discovered in our large Biodatabank and through gene\u2010matching initiatives. Patient samples were analyzed by exome\/Sanger and\n RNA<\/jats:styled-content>\n \/\n cDNA<\/jats:styled-content>\n sequencing.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We identified 16 previously unreported\n DYT<\/jats:styled-content>\n \u2010\n \n VPS16<\/jats:italic>\n <\/jats:styled-content>\n patients (7 male, median age at onset [\n AAO]<\/jats:styled-content>\n : 12\u2009years). Patients with initial leg involvement had an\n AAO<\/jats:styled-content>\n more than 10\u2009years earlier than those with involvement of the arms\/craniocervical region. Dystonia progressed in 95%, generalized in 50%, and was accompanied by pyramidal, cerebellar, or psychiatric features in 25% of patients. Two young individuals benefited greatly from timely deep brain stimulation (DBS) surgery. Of the 11 identified\n \n VPS16<\/jats:italic>\n <\/jats:styled-content>\n variants, 10 were novel. Utilizing\n RNA<\/jats:styled-content>\n \u2010Seq or\n cDNA<\/jats:styled-content>\n sequencing, we discovered alternatively spliced transcripts, thereby elucidating the effects of splice\u2010site, near\u2010splice\u2010site, and exonic variants.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n We expand the phenotypic and mutational spectrum of\n DYT<\/jats:styled-content>\n \u2010\n \n VPS16<\/jats:italic>\n <\/jats:styled-content>\n , emphasize the utility of\n RNA<\/jats:styled-content>\n \u2010Seq in clarifying\n \n VPS16<\/jats:italic>\n <\/jats:styled-content>\n variant pathogenicity, and advocate for timely DBS as a promising therapeutic option for\n DYT<\/jats:styled-content>\n \u2010\n \n VPS16<\/jats:italic>\n <\/jats:styled-content>\n patients. \u00a9 2025 The Author(s).\n Movement Disorders<\/jats:italic>\n published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mds.70089","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:15:38Z","timestamp":1762506938000},"page":"84-94","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Expanding the Genetic and Phenotypic Spectrum of\n DYT<\/scp>\n \u2010\n \n VPS16<\/i>\n <\/scp>\n : The Importance of Splice\u2010Site Variants"],"prefix":"10.1002","volume":"41","author":[{"given":"Ana","family":"Westenberger","sequence":"first","affiliation":[{"name":"Institute of Neurogenetics University of L\u00fcbeck L\u00fcbeck Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgard","family":"Verdura","sequence":"additional","affiliation":[{"name":"Therapeutics and Innovation in Pediatric Neurology Research Group Vall d'Hebron Research Institute (VHIR) Barcelona 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