{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T14:56:28Z","timestamp":1773327388171,"version":"3.50.1"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005762","name":"National Taiwan University Hospital","doi-asserted-by":"publisher","award":["113\u2010N0070"],"award-info":[{"award-number":["113\u2010N0070"]}],"id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["MOST 110\u20102314\u2010B\u2010002\u2010150\u2010MY3"],"award-info":[{"award-number":["MOST 110\u20102314\u2010B\u2010002\u2010150\u2010MY3"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p><jats:italic>IRF2BPL<\/jats:italic> mutation has been associated with a rare neurodevelopmental disorder with abnormal movements, including dystonia. However, the role of <jats:italic>IRF2BPL<\/jats:italic> in dystonia remains elusive. We aimed to investigate <jats:italic>IRF2BPL<\/jats:italic> mutations in a Taiwanese dystonia cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 300 unrelated patients with molecularly unassigned isolated (<jats:italic>n<\/jats:italic>\u2009=\u2009256) or combined dystonia (<jats:italic>n<\/jats:italic>\u2009=\u200944) were enrolled between January 2015 and July 2023. The <jats:italic>IRF2BPL<\/jats:italic> variants were analyzed based on whole exome sequencing. The in silico prediction of the identified potential pathogenic variant was performed to predict its pathogenicity. We also compared the clinical and genetic features to previous literature reports.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified one adolescent patient carrying a de novo heterozygous pathogenic variant of <jats:italic>IRF2BPL,<\/jats:italic> c.379C&gt;T (p.Gln127Ter), who presented with generalized dystonia, developmental regression, and epilepsy (0.33% of our dystonia cohort). This variant resides within the polyglutamine (poly Q) domain before the first PEST sequence block of the IRF2BPL protein, remarkably truncating the protein structure. Combined with other patients with <jats:italic>IRF2BPL<\/jats:italic> mutations in the literature (<jats:italic>n<\/jats:italic>\u2009=\u200960), patients with variants in the poly Q domain have a higher rate of nonsense mutations (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and epilepsy (<jats:italic>p<\/jats:italic>\u2009=\u20090.008) than patients with variants in other domains. Furthermore, as our index patient, carriers with substitutions before the first PEST sequence block have significantly older age of onset (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) and higher non\u2010epilepsy symptoms, including generalized dystonia (<jats:italic>p<\/jats:italic>\u2009=\u20090.003), and ataxia (<jats:italic>p<\/jats:italic>\u2009=\u20090.003).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p><jats:italic>IRF2BPL<\/jats:italic> mutation is a rare cause of dystonia in our population. Mutations in different domains of <jats:italic>IRF2BPL<\/jats:italic> exhibit different phenotypes.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.52072","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T04:23:29Z","timestamp":1713846209000},"page":"1557-1566","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic analysis of <scp><i>IRF2BPL<\/i><\/scp> in a Taiwanese dystonia cohort: The genotype and phenotype correlation"],"prefix":"10.1002","volume":"11","author":[{"given":"Pin\u2010Shiuan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology National Taiwan University Hospital  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying\u2010Fa","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology Kaohsiung Chang Gung Memorial Hospital  Kaohsiung Taiwan"},{"name":"Center for Parkinson's 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