{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:06:29Z","timestamp":1791389189889,"version":"4.3.3"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T00:00:00Z","timestamp":1529971200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"},{"start":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T00:00:00Z","timestamp":1529971200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["291924"],"award-info":[{"award-number":["291924"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012526","name":"Faculty of Health, Aarhus University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012526","id-type":"DOI","asserted-by":"publisher"}]},{"name":"John and Birthe Meyer Foundation"},{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R126-2012-1244"],"award-info":[{"award-number":["R126-2012-1244"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011102","name":"EU Seventh Framework Programme","doi-asserted-by":"publisher","award":["291924"],"award-info":[{"award-number":["291924"]}],"id":[{"id":"10.13039\/100011102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012526","name":"Faculty of Health Sciences, Aarhus University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012526","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R126\u20102012\u20101244"],"award-info":[{"award-number":["R126\u20102012\u20101244"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Lamin A\/C mutations are generally believed to be associated with a severe prognosis. The aim of this study was to investigate disease expression in three affected families carrying different LMNA missense mutations. Furthermore, the potential molecular disease mechanisms of the mutations were investigated in fibroblasts obtained from mutation carriers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>A LMNA-p.Arg216Cys missense mutation was identified in a large family with 36 mutation carriers. Disease expression was unusual with a late onset and a favourable prognosis. Two smaller families with severe disease expression were shown to carry a LMNA-p.Arg471Cys and LMNA-p.Arg471His mutation, respectively. LMNA gene and protein expression was investigated in eight different mutation carriers by quantitative reverse transcriptase polymerase chain reaction, Western blotting, immunohistochemistry, and protein mass spectrometry. The results showed that all mutation carriers incorporated mutated lamin protein into the nuclear envelope. Interestingly, the ratio of mutated to wild-type protein was only 30:70 in LMNA-p.Arg216Cys carriers with a favourable prognosis while LMNA-p.Arg471Cys and LMNA-p.Arg471His carriers with a more severe outcome expressed significantly more of the mutated protein by a ratio of 50:50.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The clinical findings indicated that some LMNA mutations may be associated with a favourable prognosis and a low risk of sudden death. Protein expression studies suggested that a severe outcome was associated with the expression of high amounts of mutated protein. These findings may prove to be helpful in counselling and risk assessment of LMNA families.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.1241","type":"journal-article","created":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T06:10:35Z","timestamp":1529993435000},"page":"1404-1412","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The clinical outcome of\n                    <i>LMNA<\/i>\n                    Missense Mutations can be Associated with the Amount of Mutated Protein in the Nuclear Envelope"],"prefix":"10.1093","volume":"20","author":[{"given":"Rasha A.","family":"Al-Saaidi","sequence":"first","affiliation":[{"name":"Research Unit for Molecular Medicine, Aarhus University and University Hospital , Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torsten B.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital , Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rune I.D.","family":"Birkler","sequence":"additional","affiliation":[{"name":"Research Unit for Molecular Medicine, Aarhus University and University Hospital , Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Palmfeldt","sequence":"additional","affiliation":[{"name":"Research Unit for Molecular Medicine, Aarhus University and University Hospital , Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelaziz","family":"Beqqali","sequence":"additional","affiliation":[{"name":"Centre for Cardiovascular Science, University of Edinburgh , Edinburgh ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yigal M.","family":"Pinto","sequence":"additional","affiliation":[{"name":"Heart Failure Research Center, Academic Medical Center , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Nissen","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Aarhus University Hospital , Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrik","family":"Baandrup","sequence":"additional","affiliation":[{"name":"Centre for Clinical Research, North Denmark Regional Hospital\/Department of Clinical Medicine, Aalborg University , Aalborg ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"M\u00f8lgaard","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital , Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas M.","family":"Hey","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Odense University Hospital , Odense ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Eiskj\u00e6r","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital , Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Bross","sequence":"additional","affiliation":[{"name":"Research Unit for Molecular Medicine, Aarhus University and University Hospital , Aarhus ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Mogensen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Odense University Hospital , Odense 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