{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T07:49:51Z","timestamp":1782460191914,"version":"3.54.5"},"reference-count":53,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T00:00:00Z","timestamp":1684281600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente 245"],"award-info":[{"award-number":["Ricerca Corrente 245"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Phospholamban is involved in the regulation of the activity and storage of calcium in cardiac muscle. Several mutations have been identified in the PLN gene causing cardiac disease associated with arrhythmogenic and dilated cardiomyopathy. The patho-mechanism underlying PLN mutations is not fully understood and a specific therapy is not yet available. PLN mutated patients have been deeply investigated in cardiac muscle, but very little is known about the effect of PLN mutations in skeletal muscle. In this study, we investigated both histological and functional features in skeletal muscle tissue and muscle-derived myoblasts from an Italian patient carrying the Arg14del mutation in PLN. The patient has a cardiac phenotype, but he also reported lower limb fatigability, cramps and fasciculations. The evaluation of a skeletal muscle biopsy showed histological, immunohistochemical and ultrastructural alterations. In particular, we detected an increase in the number of centronucleated fibers and a reduction in the fiber cross sectional area, an alteration in p62, LC3 and VCP proteins and the formation of perinuclear aggresomes. Furthermore, the patient\u2019s myoblasts showed a greater propensity to form aggresomes, even more marked after proteasome inhibition compared with control cells. Further genetic and functional studies are necessary to understand whether a definition of PLN myopathy, or cardiomyopathy plus, can be introduced for selected cases with clinical evidence of skeletal muscle involvement. Including skeletal muscle examination in the diagnostic process of PLN-mutated patients can help clarify this issue.<\/jats:p>","DOI":"10.3390\/cells12101405","type":"journal-article","created":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T06:00:29Z","timestamp":1684389629000},"page":"1405","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Characterization of Skeletal Muscle Biopsy and Derived Myoblasts in a Patient Carrying Arg14del Mutation in Phospholamban Gene"],"prefix":"10.3390","volume":"12","author":[{"given":"Simona","family":"Zanotti","sequence":"first","affiliation":[{"name":"Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Salani","sequence":"additional","affiliation":[{"name":"Neurology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Ciscato","sequence":"additional","affiliation":[{"name":"Neuromuscular and Rare Disease Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6877-0288","authenticated-orcid":false,"given":"Silvia","family":"Priori","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Pavia, 27100 Pavia, Italy"},{"name":"Department of Molecular Cardiology, IRCCS ICS Maugeri, 27100 Pavia, Italy"},{"name":"Laboratory of Molecular Cardiology, Centro Nacional de Investigaciones 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Rathod, N., Bak, J.J., Primeau, J.O., Fisher, M.E., Espinoza-Fonseca, L.M., Lemieux, M.J., and Young, H.S. 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