{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T06:20:35Z","timestamp":1778653235696,"version":"3.51.4"},"reference-count":48,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2017,5,15]],"date-time":"2017-05-15T00:00:00Z","timestamp":1494806400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neuromuscular Diseases"],"published-print":{"date-parts":[[2017,5,30]]},"abstract":"<jats:p>\n                    Background: Central core disease and malignant hyperthermia are human disorders of skeletal muscle resulting from aberrant Ca\n                    <jats:sup>2+<\/jats:sup>\n                    handling. Most malignant hyperthermia and central core disease cases are associated with amino acid changes in the type 1 ryanodine receptor (RyR1), the skeletal muscle Ca\n                    <jats:sup>2+<\/jats:sup>\n                    -release channel. Malignant hyperthermia exhibits a gain-of-function phenotype, and central core disease results from loss of channel function. For a variant to be classified as pathogenic, functional studies must demonstrate a correlation with the pathophysiology of malignant hyperthermia or central core disease.\n                  <\/jats:p>\n                  <jats:p>Objective: We assessed the pathogenicity of four C-terminal variants of the ryanodine receptor using functional analysis. The variants were identified in families affected by either malignant hyperthermia or central core disease.<\/jats:p>\n                  <jats:p>Methods: Four variants were introduced separately into human cDNA encoding the skeletal muscle ryanodine receptor. Following transient expression in HEK-293T cells, functional studies were carried out using calcium release assays in response to an agonist. Two previously characterized variants and wild-type skeletal muscle ryanodine receptor were used as controls.<\/jats:p>\n                  <jats:p>Results: The p.Met4640Ile variant associated with central core disease showed no difference in calcium release compared to wild-type. The p.Val4849Ile variant associated with malignant hyperthermia was more sensitive to agonist than wild-type but did not reach statistical significance and two variants (p.Phe4857Ser and p.Asp4918Asn) associated with central core disease were completely inactive.<\/jats:p>\n                  <jats:p>Conclusions: The p.Val4849Ile variant should be considered a risk factor for malignant hyperthermia, while the p.Phe4857Ser and p.Asp4918Asn variants should be classified as pathogenic for central core disease.<\/jats:p>","DOI":"10.3233\/jnd-170210","type":"journal-article","created":{"date-parts":[[2017,5,16]],"date-time":"2017-05-16T12:56:20Z","timestamp":1494939380000},"page":"147-158","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["Functional Characterization of C-terminal Ryanodine Receptor 1 Variants Associated with Central Core Disease or Malignant Hyperthermia"],"prefix":"10.1177","volume":"4","author":[{"given":"Remai","family":"Parker","sequence":"first","affiliation":[{"name":"Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja H.","family":"Schiemann","sequence":"additional","affiliation":[{"name":"Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elaine","family":"Langton","sequence":"additional","affiliation":[{"name":"Wellington Hospital, Wellington, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Terasa","family":"Bulger","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Intensive Care, Palmerston North Hospital, Palmerston North, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neil","family":"Pollock","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Intensive Care, Palmerston North Hospital, Palmerston North, New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Bjorksten","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Melbourne"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robyn","family":"Gillies","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Melbourne"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Auckland City Hospital, Auckland, New 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