{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T19:34:02Z","timestamp":1790278442879,"version":"4.1.0"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,8,26]],"date-time":"2021-08-26T00:00:00Z","timestamp":1629936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente 5x1000"],"award-info":[{"award-number":["Ricerca Corrente 5x1000"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction\/Aims<\/jats:title><jats:p>Stromal interaction molecule 1 (STIM1) is a reticular Ca<jats:sup>2+<\/jats:sup> sensor composed of a luminal and a cytosolic domain. Autosomal dominant mutations in <jats:italic>STIM1<\/jats:italic> cause tubular aggregate myopathy and Stormorken syndrome or its variant York platelet syndrome. In this study we aimed to expand the features related to new variants in <jats:italic>STIM1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a cross\u2010sectional study of individuals harboring monoallelic <jats:italic>STIM1<\/jats:italic> variants recruited at five tertiary centers involved in a study of inherited myopathies analyzed with a multigene\u2010targeted panel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified seven individuals (age range, 26\u201057\u2009years) harboring variants in <jats:italic>STIM1<\/jats:italic>, including five novel changes: three located in the EF\u2010hand domain, one in the sterile \u03b1 motif (SAM) domain, and one in the cytoplasmatic region of the protein. Functional evaluation of the pathogenic variants using a heterologous expression system and measuring store\u2010operated calcium entry demonstrated their causative role and suggested a link of new variants with the clinical phenotype. Muscle contractures, found in three individuals, showed variability in body distribution and in the number of joints involved. Three patients showed cardiac and respiratory involvement. Short stature, hyposplenism, sensorineural hearing loss, hypothyroidism, and Gilbert syndrome were variably observed among the patients. Laboratory tests revealed hyperCKemia in six patients, thrombocytopenia in two patients, and hypocalcemia in one patient. Muscle biopsy showed the presence of tubular aggregates in three patients, type I fiber atrophy in one patient, and nonspecific myopathic changes in two patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our clinical, histological, and molecular data expand the genetic and clinical spectrum of <jats:italic>STIM1\u2010<\/jats:italic>related diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mus.27391","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T05:01:35Z","timestamp":1628485295000},"page":"567-575","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Expanding the clinical and genetic spectrum of pathogenic variants in <scp><i>STIM1<\/i><\/scp>"],"prefix":"10.1002","volume":"64","author":[{"given":"Chiara","family":"Ticci","sequence":"first","affiliation":[{"name":"IRCCS Fondazione Stella Maris Molecular Medicine Laboratory  Pisa Italy"},{"name":"AOU Meyer  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Cassandrini","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Stella Maris Molecular Medicine Laboratory  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Rubegni","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Stella Maris Molecular Medicine Laboratory  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Riva","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Universit\u00e0 del Piemonte Orientale  Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3412-8339","authenticated-orcid":false,"given":"Gaetano","family":"Vattemi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine and Movement Sciences University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Mat\u00e0","sequence":"additional","affiliation":[{"name":"Careggi University Hospital, Neurology Unit  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Ricci","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Baldacci","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Stella Maris Molecular Medicine Laboratory  Pisa Italy"},{"name":"Kode s.r.l.  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Guglielmi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine and Movement Sciences University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Di Muzio","sequence":"additional","affiliation":[{"name":"Department of Neurology SS Annunziata Hospital  Chieti Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Malandrini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences University of Siena  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Tonin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Biomedicine and Movement Sciences University of Verona  Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriele","family":"Siciliano","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Federico","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neurosciences University of Siena  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando A.","family":"Genazzani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Universit\u00e0 del Piemonte Orientale  Novara Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filippo M.","family":"Santorelli","sequence":"additional","affiliation":[{"name":"IRCCS Fondazione Stella Maris Molecular Medicine Laboratory  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Merlini","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Neuromotor Sciences University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,8,26]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12938"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-2888-2_15"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608247200"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1842"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.05.020"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102623"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2011.10.005"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1649920"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1312520111"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22544"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2016.10.006"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.12.307"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2010.01.011"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-018-0863-x"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000352"},{"key":"e_1_2_10_17_1","unstructured":"https:\/\/cadd.gs.washington.edu\/snv. 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