{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:48:54Z","timestamp":1790790534926,"version":"4.1.0"},"reference-count":37,"publisher":"Portland Press Ltd.","issue":"7","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002889","name":"Foundation for Prader-Willi Research","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100002889","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Prader\u2013Willi syndrome (PWS) and Schaaf\u2013Yang syndrome (SYS) share overlapping phenotypic features, but potential cardiac involvement in both conditions remains poorly understood. Here, we investigated cardiac function in Magel2 knockout (KO) mice, a model relevant to PWS and SYS, to assess the impact of Magel2 deficiency on the heart. Echocardiographic analysis of 20-week-old Magel2-KO mice revealed concentric remodeling of the left ventricle together with reduced left ventricular end-diastolic volume and stroke volume, as well as a modest but significant reduction in ejection fraction. Electrophysiological studies identified sex-dependent alterations, particularly in males, characterized by shortened action potential duration and increased atrial potassium currents. Surface electrocardiography recordings showed no overt arrhythmias and visual inspection confirmed sinus rhythm during the monitoring period; however, the observed cellular alterations indicate increased arrhythmogenic susceptibility. In addition, aged Magel2-KO mice developed adult-onset obesity and exhibited elevated HbA1c levels consistent with impaired glycemic control. Given the minimal expression of Magel2 in cardiac tissue, these findings suggest that systemic and metabolic alterations may contribute to the observed cardiac phenotype. Together, these results demonstrate structural cardiac remodeling and electrophysiological changes consistent with increased arrhythmogenic susceptibility in Magel2-deficient mice, suggesting clinically relevant cardiac involvement in SYS and PWS. Our findings support consideration of structured cardiovascular monitoring to mitigate potential secondary cardiac complications in affected individuals.<\/jats:p>","DOI":"10.1042\/cs20260647","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T16:17:36Z","timestamp":1781194656000},"page":"1415-1427","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Magel2 deficiency promotes cardiac remodeling and increases arrhythmogenic susceptibility in a mouse model relevant to Prader\u2013Willi and Schaaf\u2013Yang syndromes"],"prefix":"10.1042","volume":"140","author":[{"given":"Laura","family":"D\u00f6tsch","sequence":"first","affiliation":[{"name":"1Institute of Human Genetics, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Weirauch","sequence":"additional","affiliation":[{"name":"2Department of Internal Medicine III, University Hospital Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janika","family":"Hunger","sequence":"additional","affiliation":[{"name":"1Institute of Human Genetics, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Thiemann","sequence":"additional","affiliation":[{"name":"2Department of Internal Medicine III, University Hospital Heidelberg, Germany"},{"name":"3German Centre for Cardiovascular Research (DZHK), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johann","family":"Maa\u00df","sequence":"additional","affiliation":[{"name":"1Institute of Human Genetics, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5897-237X","authenticated-orcid":false,"given":"Constanze","family":"Schmidt","sequence":"additional","affiliation":[{"name":"2Department of Internal Medicine III, University Hospital Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1157-474X","authenticated-orcid":false,"given":"Florian","family":"Leuschner","sequence":"additional","affiliation":[{"name":"2Department of Internal Medicine III, University Hospital Heidelberg, Germany"},{"name":"3German Centre for Cardiovascular Research (DZHK), Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2148-7490","authenticated-orcid":false,"given":"Christian\u00a0P.","family":"Schaaf","sequence":"additional","affiliation":[{"name":"1Institute of Human Genetics, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9757-2034","authenticated-orcid":false,"given":"Henning","family":"Fr\u00f6hlich","sequence":"additional","affiliation":[{"name":"1Institute of Human Genetics, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"2026062208213441100_B1","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1097\/YCO.0000000000000981","article-title":"Genetics of Prader\u2013Willi and Angelman syndromes: 2024 update","volume":"38","author":"Godler","year":"2025","journal-title":"Curr. 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