{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T08:40:40Z","timestamp":1784882440795,"version":"3.55.0"},"reference-count":46,"publisher":"Elsevier BV","issue":"12","license":[{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,12,1]],"date-time":"2023-12-01T00:00:00Z","timestamp":1701388800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T00:00:00Z","timestamp":1698883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","nmd-journal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Neuromuscular Disorders"],"published-print":{"date-parts":[[2023,12]]},"DOI":"10.1016\/j.nmd.2023.10.019","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T05:13:20Z","timestamp":1698988400000},"page":"951-963","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"title":["Functional characterization of RYR1 variants identified in malignant hyperthermia susceptible individuals"],"prefix":"10.1016","volume":"33","author":[{"given":"Yuko","family":"Noda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotsugu","family":"Miyoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia","family":"Benucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asensio","family":"Gonzalez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Bandschapp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Girard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0007-9631","authenticated-orcid":false,"given":"Susan","family":"Treves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Zorzato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.nmd.2023.10.019_bib0001","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/S0140-6736(98)03078-5","article-title":"Malignant hyperthermia","volume":"352","author":"Denborough","year":"1998","journal-title":"Lancet"},{"key":"10.1016\/j.nmd.2023.10.019_bib0002","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1126\/science.256.5058.789","article-title":"Malignant hyperthermia","volume":"256","author":"MacLennan","year":"1992","journal-title":"Science"},{"key":"10.1016\/j.nmd.2023.10.019_bib0003","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/S0196-0644(87)80235-4","article-title":"Malignant hyperthermia","volume":"16","author":"Tomarken","year":"1987","journal-title":"Ann Emerg Med"},{"key":"10.1016\/j.nmd.2023.10.019_bib0004","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1213\/ANE.0000000000006207","article-title":"Oral dantrolene for myopathic symptoms in malignant hyperthermia-susceptible patients: a 25-year retrospective cohort study of adverse effects and tolerability","volume":"136","author":"Ibarra Moreno","year":"2023","journal-title":"Anesth Analg"},{"key":"10.1016\/j.nmd.2023.10.019_bib0005","doi-asserted-by":"crossref","first-page":"2","DOI":"10.2174\/1381612827666210804095300","article-title":"RYR1-related rhabdomyolysis: a spectrum of hypermetabolic states due to ryanodine receptor dysfunction","volume":"28","author":"Krujit","year":"2022","journal-title":"Curr Pharm Des"},{"key":"10.1016\/j.nmd.2023.10.019_bib0006","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0014-2999(90)94788-Y","article-title":"Inhibitory action of dantrolene on Ca-induced Ca2+ release from sarcoplasmic reticulum in guinea pig skeletal muscle","volume":"178","author":"Ohta","year":"1990","journal-title":"Eur J Pharmacol"},{"key":"10.1016\/j.nmd.2023.10.019_bib0007","doi-asserted-by":"crossref","first-page":"18465","DOI":"10.1074\/jbc.270.31.18465","article-title":"Identification of dantrolene binding sites in porcine skeletal muscle sarcoplasmic reticulum","volume":"270","author":"Parness","year":"1995","journal-title":"J Biol Chem"},{"key":"10.1016\/j.nmd.2023.10.019_bib0008","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1177\/0310057X211053644","article-title":"The effects of dantrolene in the presence or absence of ryanodine receptor type 1 variants in individuals predisposed to malignant hyperthermia","volume":"50","author":"Noda","year":"2022","journal-title":"Anaesth Intensive Care"},{"key":"10.1016\/j.nmd.2023.10.019_bib0009","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1034\/j.1399-6576.2002.460914.x","article-title":"Reproducibility of in vitro contracture test results in patients tested for malignant hyperthermia susceptibility","volume":"46","author":"Islander","year":"2002","journal-title":"Acta Anaesthesiol Scand"},{"key":"10.1016\/j.nmd.2023.10.019_bib0010","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1093\/bja\/aev225","article-title":"European malignant hyperthermia group guidelines for investigation of malignant hyperthermia susceptibility","volume":"115","author":"Hopkins","year":"2015","journal-title":"Br J Anaesth"},{"key":"10.1016\/j.nmd.2023.10.019_bib0011","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/sj.ejhg.5200964","article-title":"Recent advances in the diagnosis of malignant hyperthermia susceptibility: how confident can we be of genetic testing?","volume":"11","author":"Robinson","year":"2003","journal-title":"Eur J Hum Genet"},{"key":"10.1016\/j.nmd.2023.10.019_bib0012","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1152\/physiolgenomics.00126.2016","article-title":"Pharmacogenetics and pathophysiology of CACNA1S mutations in malignant hyperthermia","volume":"49","author":"Beam","year":"2017","journal-title":"Physiol Genomics"},{"key":"10.1016\/j.nmd.2023.10.019_bib0013","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.bja.2018.06.028","article-title":"Genetic epidemiology of malignant hyperthermia in the UK","volume":"121","author":"Miller","year":"2018","journal-title":"Br J Anaesth"},{"key":"10.1016\/j.nmd.2023.10.019_bib0014","doi-asserted-by":"crossref","DOI":"10.1186\/s13023-015-0310-1","article-title":"Malignant hyperthermia: a review","author":"Rosenberg","year":"2015","journal-title":"Orphanet J Rare Dis"},{"key":"10.1016\/j.nmd.2023.10.019_bib0015","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/s41436-021-01125-w","article-title":"Variant curation expert panel recommendations for RYR1 pathogenicity classifications in malignant Hyperthermia susceptibility","volume":"23","author":"Johnston","year":"2021","journal-title":"Genet Med"},{"key":"10.1016\/j.nmd.2023.10.019_bib0016","doi-asserted-by":"crossref","DOI":"10.3389\/fgene.2022.1010327","article-title":"Insights on variant analysis in silico tools for pathogenicity prediction","volume":"13","author":"Garcia","year":"2022","journal-title":"Front Genet"},{"issue":"9","key":"10.1016\/j.nmd.2023.10.019_bib0017","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1038\/gim.2017.210","article-title":"Modeling the ACMG\/AMP variant classification guidelines as Bayesian classification frameworks","volume":"20","author":"Tavtigian","year":"2018","journal-title":"Genet Med"},{"key":"10.1016\/j.nmd.2023.10.019_bib0018","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1172\/JCI993","article-title":"Intracellular calcium homeostasis in human primary muscle cells from malignant hyperthermia-susceptible and normal individuals. Effect Of overexpression of recombinant wild-type and Arg163Cys mutated ryanodine receptors","volume":"101","author":"Censier","year":"1998","journal-title":"J Clin Invest"},{"key":"10.1016\/j.nmd.2023.10.019_bib0019","doi-asserted-by":"crossref","first-page":"43838","DOI":"10.1074\/jbc.M403612200","article-title":"Effect of ryanodine receptor mutations on interleukin-6 release and intracellular calcium homeostasis in human myotubes from malignant hyperthermia-susceptible individuals and patients affected by central core disease","volume":"279","author":"Ducreux","year":"2004","journal-title":"J Biol Chem"},{"key":"10.1016\/j.nmd.2023.10.019_bib0020","doi-asserted-by":"crossref","DOI":"10.3791\/62196","article-title":"Functional characterization of endogenously expressed human RYR1 variants","author":"Treves","year":"2021","journal-title":"J Vis Exp"},{"key":"10.1016\/j.nmd.2023.10.019_bib0021","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1054\/ceca.2001.0252","article-title":"Functional properties of EGFP-tagged skeletal muscle calcium-release channel (ryanodine receptor) expressed in COS-7 cells: sensitivity to caffeine and 4-chloro-m-cresol","volume":"31","author":"Treves","year":"2001","journal-title":"Cell Calcium"},{"key":"10.1016\/j.nmd.2023.10.019_bib0022","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1042\/bj3010661","article-title":"Alteration of intracellular Ca2+ transients in COS-7 cells transfected with the cDNA encoding skeletal-muscle ryanodine receptor carrying a mutation associated with malignant hyperthermia","volume":"301","author":"Treves","year":"1994","journal-title":"Biochem J"},{"key":"10.1016\/j.nmd.2023.10.019_bib0023","doi-asserted-by":"crossref","first-page":"4636","DOI":"10.1093\/hmg\/ddv195","article-title":"Epigenetic changes as a common trigger of muscle weakness in congenitl myopathies","volume":"24","author":"Rokach","year":"2015","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.nmd.2023.10.019_bib0024","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"EUCSF Chimera\u2013a visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J Comput Chem"},{"key":"10.1016\/j.nmd.2023.10.019_bib0025","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.str.2011.03.019","article-title":"A smoothed backbone-dependent rotamer library for proteins derived from adaptive kernel density estimates and regressions","volume":"19","author":"Shapovalov","year":"2011","journal-title":"Structure"},{"key":"10.1016\/j.nmd.2023.10.019_bib0026","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.cell.2016.08.075","article-title":"Structural basis for gating and activation of RyR1","volume":"167","author":"des Georges","year":"2016","journal-title":"Cell"},{"issue":"D1","key":"10.1016\/j.nmd.2023.10.019_bib0027","doi-asserted-by":"crossref","first-page":"D520","DOI":"10.1093\/nar\/gky949","article-title":"Protein Data Bank: the single global archive for 3D macromolecular structure data","volume":"47","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"10.1016\/j.nmd.2023.10.019_bib0028","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1002\/humu.20878","article-title":"Increasing the number of diagnostic mutations in malignant hyperthermia","volume":"30","author":"Levano","year":"2009","journal-title":"Hum Mutat"},{"key":"10.1016\/j.nmd.2023.10.019_bib0029","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1002\/humu.20231","article-title":"Correlations between genotype and pharmacological, functional, and clinical phenotypes in malignant hyperthermia susceptibility","volume":"26","author":"Monnier","year":"2005","journal-title":"Hum Mutat"},{"key":"10.1016\/j.nmd.2023.10.019_bib0030","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1001\/jamaophthalmol.2013.4392","article-title":"RYR1 mutations as a cause of ophthalmoplegia, facial weakness, and malignant hyperthermia","volume":"13","author":"Shaaban","year":"2013","journal-title":"JAMA Ophthalmol"},{"key":"10.1016\/j.nmd.2023.10.019_bib0031","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.ajhg.2016.08.016","article-title":"REVEL: an ensemble method for predicting the pathogenicity of rare missense variants","volume":"99","author":"Ioannidis","year":"2016","journal-title":"Am J Hum Genet"},{"key":"10.1016\/j.nmd.2023.10.019_bib0032","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/humu.22209","article-title":"JP-45\/JSRP1 variants affect skeletal muscle excitation-contraction coupling by decreasing the sensitivity of the dihydropyridine receptor","volume":"34","author":"Yasuda","year":"2013","journal-title":"Hum Mutat"},{"key":"10.1016\/j.nmd.2023.10.019_bib0033","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1093\/hmg\/ddl221","article-title":"Characterization of recessive RYR1 mutations in core myopathies","volume":"15","author":"Zhou","year":"2006","journal-title":"Hum Mol Genet"},{"key":"10.1016\/j.nmd.2023.10.019_bib0034","doi-asserted-by":"crossref","first-page":"48077","DOI":"10.1074\/jbc.M107134200","article-title":"B-lymphocytes from malignant hyperthermia-susceptible patients have an increased sensitivity to skeletal muscle ryanodine receptor activators","volume":"276","author":"Girard","year":"2001","journal-title":"J Biol Chem"},{"key":"10.1016\/j.nmd.2023.10.019_bib0035","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1042\/BJ20051282","article-title":"Functional properties of ryanodine receptors carrying three amino acid substitutions identified in patients affected by multi-minicore disease and central core disease, expressed in immortalized lymphocytes","volume":"395","author":"Ducreux","year":"2006","journal-title":"Biochem J"},{"key":"10.1016\/j.nmd.2023.10.019_bib0036","doi-asserted-by":"crossref","first-page":"37471","DOI":"10.1074\/jbc.M701379200","article-title":"Enhanced excitation-coupled calcium entry in myotubes is associated with expression of RyR1 malignant hyperthermia mutations","volume":"282","author":"Yang","year":"2007","journal-title":"J Biol Chem"},{"key":"10.1016\/j.nmd.2023.10.019_bib0037","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1085\/jgp.118.3.277","article-title":"Functional effects of central core disease mutations in the cytoplasmic region of the skeletal muscle ryanodine receptor","volume":"118","author":"Avila","year":"2001","journal-title":"J Gen Physiol"},{"key":"10.1016\/j.nmd.2023.10.019_bib0038","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1124\/mol.110.067959","article-title":"Functional and biochemical properties of ryanodine receptor type 1 channels from heterozygous R163C malignant hyperthermia-susceptible mice","volume":"79","author":"Feng","year":"2011","journal-title":"Mol Pharmacol"},{"key":"10.1016\/j.nmd.2023.10.019_bib0039","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1096\/fj.11-197582","article-title":"Mice expressing T4826I-RYR1 are viable but exhibit sex- and genotype-dependent susceptibility to malignant hyperthermia and muscle damage","volume":"26","author":"Yuen","year":"2012","journal-title":"FASEB J"},{"key":"10.1016\/j.nmd.2023.10.019_bib0040","doi-asserted-by":"crossref","first-page":"4087","DOI":"10.1093\/hmg\/ddac145","article-title":"Updated variant curation expert panel criteria and pathogenicity classifications for 251 variants for RYR1-related malignant hyperthermia susceptibility","volume":"31","author":"Johnston","year":"2022","journal-title":"Hum Mol Genet"},{"issue":"5","key":"10.1016\/j.nmd.2023.10.019_bib0041","doi-asserted-by":"crossref","first-page":"e49891","DOI":"10.15252\/embr.201949891","article-title":"Structure of RyR1 in native membranes","volume":"21","author":"Chen","year":"2020","journal-title":"EMBO Rep"},{"key":"10.1016\/j.nmd.2023.10.019_bib0042","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2022.870285","article-title":"Correlation of phenotype-genotype and protein structure in RYR1-related myopathy","volume":"13","author":"Chang","year":"2022","journal-title":"Front Neurol"},{"issue":"1","key":"10.1016\/j.nmd.2023.10.019_bib0043","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1186\/s40478-021-01287-3","article-title":"RyR1-related myopathy mutations in ATP and calcium binding sites impair channel regulation","volume":"9","author":"Yuan","year":"2021","journal-title":"Acta Neuropathol Commun"},{"key":"10.1016\/j.nmd.2023.10.019_bib0044","doi-asserted-by":"crossref","first-page":"17535","DOI":"10.1074\/jbc.M115.659672","article-title":"Channel gating dependence on pore lining helix glycine residues in skeletal muscle ryanodine receptor","volume":"290","author":"Mei","year":"2015","journal-title":"J Biol Chem"},{"key":"10.1016\/j.nmd.2023.10.019_bib0045","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1074\/jbc.M117.803247","article-title":"G4941K substitution in the pore-lining S6 helix of the skeletal muscle ryanodine receptor increases RyR1 sensitivity to cytosolic and lumina, Ca2+","volume":"293","author":"Xu","year":"2018","journal-title":"J Biol Chem"},{"key":"10.1016\/j.nmd.2023.10.019_bib0046","doi-asserted-by":"crossref","first-page":"284","DOI":"10.3389\/fphar.2015.00284","article-title":"The hydrophobic effect contributes to the closed state of a simplified ion channel through a conserved hydrophobic patch at the pore-helix crossing","volume":"6","author":"Yonkunas","year":"2015","journal-title":"Front Pharmacol"}],"container-title":["Neuromuscular Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960896623007721?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960896623007721?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T08:14:37Z","timestamp":1760775277000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960896623007721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12]]},"references-count":46,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2023,12]]}},"alternative-id":["S0960896623007721"],"URL":"https:\/\/doi.org\/10.1016\/j.nmd.2023.10.019","relation":{},"ISSN":["0960-8966"],"issn-type":[{"value":"0960-8966","type":"print"}],"subject":[],"published":{"date-parts":[[2023,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Functional characterization of RYR1 variants identified in malignant hyperthermia susceptible individuals","name":"articletitle","label":"Article Title"},{"value":"Neuromuscular Disorders","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.nmd.2023.10.019","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Author(s). Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}