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The age at onset of<jats:italic>RYR1<\/jats:italic>-related myopathies varies from infancy to adulthood. We report the identification of four<jats:italic>RYR1<\/jats:italic>variants in two Italian families: one with myopathy and variants c.4003C&gt;T (p.R1335C) and c.7035C&gt;A (p.S2345R), and another with CCD and variants c.9293G&gt;T (p.S3098I) and c.14771_14772insTAGACAGGGTGTTGCTCTGTTGCCCTTCTT (p.F4924_V4925insRQGVALLPFF). We demonstrate that, in patient-specific lymphoblastoid cells, the c.4003C&gt;T (p.R1335C) variant is not expressed and the in-frame 30-nucleotide insertion variant is expressed at a low level. Moreover, Ca<jats:sup>2+<\/jats:sup>release in response to the RyR1 agonist 4-chloro-m-cresol and to thapsigargin showed that the c.7035C&gt;A (p.S2345R) variant causes depletion of S\/ER Ca<jats:sup>2+<\/jats:sup>stores and that the compound heterozygosity for variant c.9293G&gt;T (p.S3098I) and the 30-nucleotide insertion increases RyR1-dependent Ca<jats:sup>2+<\/jats:sup>release without affecting ER Ca<jats:sup>2+<\/jats:sup>stores. In conclusion, we detected and functionally characterized disease-causing variants of the RyR1 channel in patient-specific lymphoblastoid cells.<\/jats:p>","DOI":"10.1155\/2019\/7638946","type":"journal-article","created":{"date-parts":[[2019,4,21]],"date-time":"2019-04-21T23:31:38Z","timestamp":1555889498000},"page":"1-13","source":"Crossref","is-referenced-by-count":13,"title":["<i>RYR1<\/i>Sequence Variants in Myopathies: Expression and Functional Studies in Two Families"],"prefix":"10.1155","volume":"2019","author":[{"given":"Alberto","family":"Zullo","sequence":"first","affiliation":[{"name":"CEINGE-Advanced Biotechnologies, Via Gaetano Salvatore 486, 80145 Naples, Italy"},{"name":"Department of Sciences and Technologies, University of Sannio, Via Port\u2019Arsa 11, 82100 Benevento, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppa","family":"Perrotta","sequence":"additional","affiliation":[{"name":"CEINGE-Advanced Biotechnologies, Via Gaetano 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