{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T16:49:30Z","timestamp":1761324570908,"version":"build-2065373602"},"reference-count":19,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T00:00:00Z","timestamp":1710460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of L\u00fcbeck"},{"name":"Durham University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Muscles"],"abstract":"<jats:p>SYNE2 mutations have been associated with skeletal and cardiac muscle diseases, including Emery-Dreifuss muscular dystrophy (EDMD). Here, we present a 70-year-old male patient with muscle pain and elevated serum creatine kinase levels in whom whole-exome sequencing revealed a novel heterozygous SYNE2 splice site mutation (NM_182914.3:c.15306+2T&gt;G). This mutation is likely to result in the loss of the donor splice site in intron 82. While a diagnostic muscle biopsy showed unspecific myopathological findings, immunofluorescence analyses of skeletal muscle and dermal cells derived from the patient showed nuclear shape alterations when compared to control cells. In addition, a significantly reduced nesprin-2 giant protein localisation to the nuclear envelope was observed in patient-derived dermal fibroblasts. Our findings imply that the novel heterozygous SYNE2 mutation results in a monoallelic splicing defect of nesprin-2, thereby leading to a rare cause of myalgia and hyperCKemia.<\/jats:p>","DOI":"10.3390\/muscles3010010","type":"journal-article","created":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T08:17:29Z","timestamp":1710749849000},"page":"100-109","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An Intronic Heterozygous SYNE2 Splice Site Mutation: A Rare Cause for Myalgia and hyperCKemia?"],"prefix":"10.3390","volume":"3","author":[{"given":"Theresa","family":"Paulus","sequence":"first","affiliation":[{"name":"Department of Neurology, University of L\u00fcbeck, Ratzeburger Allee 160, 23538 L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Young","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Durham University, South Road, Durham DH1 3LE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Jessop","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Durham University, South Road, Durham DH1 3LE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolin","family":"Berwanger","sequence":"additional","affiliation":[{"name":"Institute of Aerospace Medicine, German Aerospace Center, Linder H\u00f6he, 51147 Cologne, Germany"},{"name":"Center for Physiology and Pathophysiology, Institute of Vegetative Physiology, Medical Faculty, University of Cologne, Robert-Koch-Stra\u00dfe 39, 50931 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1291-4219","authenticated-orcid":false,"given":"Christoph Stephan","family":"Clemen","sequence":"additional","affiliation":[{"name":"Institute of Aerospace Medicine, German Aerospace Center, Linder H\u00f6he, 51147 Cologne, Germany"},{"name":"Center for Physiology and Pathophysiology, Institute of Vegetative Physiology, Medical Faculty, University of Cologne, Robert-Koch-Stra\u00dfe 39, 50931 Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf","family":"Schr\u00f6der","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-N\u00fcrnberg, Schwabachanlage 6, 91054 Erlangen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6286-5526","authenticated-orcid":false,"given":"Rafal","family":"Ploski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Medical University of Warsaw, Pawi\u0144skiego 3c, 02-106 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Hagel","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Martinistra\u00dfe 52, 20251 Hamburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yorck","family":"Hellenbroich","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University of L\u00fcbeck, Ratzeburger Allee 160, 23538 L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0241-0612","authenticated-orcid":false,"given":"Andreas","family":"Moser","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of L\u00fcbeck, Ratzeburger Allee 160, 23538 L\u00fcbeck, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iakowos","family":"Karakesisoglou","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Durham University, South Road, Durham DH1 3LE, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.yexcr.2016.06.008","article-title":"N-terminal nesprin-2 variants regulate \u03b2-catenin signalling","volume":"345","author":"Zhang","year":"2016","journal-title":"Exp. 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