{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:50:59Z","timestamp":1753890659939,"version":"3.41.2"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T00:00:00Z","timestamp":1707350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008537","name":"Benign Essential Blepharospasm Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008537","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontierspartnerships.org"],"crossmark-restriction":true},"short-container-title":["Dystonia"],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> In preceding work, a deleterious <jats:italic>REEP4<\/jats:italic> variant [GRCh38\/hg38, NC_000008.11:g.22140245G&amp;gt;A, NM_025232.4:c.109C&amp;gt;T, p.Arg37Trp] was found to co-segregate with blepharospasm (BSP) in a large African-American pedigree. Other <jats:italic>REEP4<\/jats:italic> variants have been reported in genetic screening studies of dystonia. The <jats:italic>REEP4<\/jats:italic> paralogs, <jats:italic>REEP1<\/jats:italic> and <jats:italic>REEP2<\/jats:italic>, are associated with spastic paraplegia. The causal contributions of <jats:italic>REEP4<\/jats:italic> variants to dystonia and other neurological disorders remains indecisive.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Sanger sequencing was used to screen subjects (<jats:italic>N<\/jats:italic> = 307) with BSP and BSP-plus dystonia affecting additional anatomical segments (BSP+) phenotypes for variants in <jats:italic>REEP4<\/jats:italic>. <jats:italic>In silico<\/jats:italic> tools were used to examine the deleteriousness of reported (ClinVar) and previously published <jats:italic>REEP4<\/jats:italic> variants.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> No highly deleterious variant was identified in coding or contiguous splice site regions of <jats:italic>REEP4<\/jats:italic> in our cohort of 307 subjects. <jats:italic>In silico<\/jats:italic> analysis identified numerous deleterious <jats:italic>REEP4<\/jats:italic> variants in published screening studies of dystonia and several highly deleterious single nucleotide <jats:italic>REEP4<\/jats:italic> variants in ClinVar.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Highly deleterious <jats:italic>REEP4<\/jats:italic> variants are rare in BSP and BSP+ phenotypes.<\/jats:p>","DOI":"10.3389\/dyst.2024.12016","type":"journal-article","created":{"date-parts":[[2024,2,8]],"date-time":"2024-02-08T14:24:00Z","timestamp":1707402240000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["REEP4 variant analysis in blepharospasm and other neurological disorders"],"prefix":"10.3389","volume":"3","author":[{"given":"Samira","family":"Saeirad","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark 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