{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:20:04Z","timestamp":1787026804152,"version":"build-2736575974"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,3,5]],"date-time":"2018-03-05T00:00:00Z","timestamp":1520208000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"publisher","award":["Bench-to-Bedside Program"],"award-info":[{"award-number":["Bench-to-Bedside Program"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["National Institute of Nursing Research Intramural Program"],"award-info":[{"award-number":["National Institute of Nursing Research Intramural Program"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"DOI":"10.3389\/fneur.2018.00118","type":"journal-article","created":{"date-parts":[[2018,3,5]],"date-time":"2018-03-05T02:47:39Z","timestamp":1520218059000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Novel Variants in Individuals with RYR1-Related Congenital Myopathies: Genetic, Laboratory, and Clinical Findings"],"prefix":"10.3389","volume":"9","author":[{"given":"Joshua J.","family":"Todd","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muslima S.","family":"Razaqyar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica W.","family":"Witherspoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tokunbor A.","family":"Lawal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ami","family":"Mankodi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene C.","family":"Chrismer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary D.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique S.","family":"Shelton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Amburgey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitriy","family":"Niyazov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Fequiere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten G.","family":"B\u00f6nnemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James J.","family":"Dowling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine G.","family":"Meilleur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,3,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1002\/ana.22510","article-title":"Prevalence of congenital myopathies in a representative pediatric united states population","volume":"70","author":"Amburgey","year":"2011","journal-title":"Ann Neurol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s11910-008-0012-3","article-title":"Congenital myopathies","volume":"8","author":"D\u2019Amico","year":"2008","journal-title":"Curr Neurol Neurosci Rep"},{"key":"B3","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/s40478-016-0392-6","article-title":"Review of RyR1 pathway and associated pathomechanisms","volume":"4","author":"Witherspoon","year":"2016","journal-title":"Acta Neuropathol Commun"},{"key":"B4","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1006\/geno.1996.0238","article-title":"The structural organization of the human skeletal muscle ryanodine receptor (RYR1) gene","volume":"34","author":"Phillips","year":"1996","journal-title":"Genomics"},{"key":"B5","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/nature13950","article-title":"Structure of a mammalian ryanodine receptor","volume":"517","author":"Zalk","year":"2015","journal-title":"Nature"},{"key":"B6","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1002\/humu.22056","article-title":"Clinical and genetic findings in a large cohort of patients with ryanodine receptor 1 gene-associated myopathies","volume":"33","author":"Klein","year":"2012","journal-title":"Hum Mutat"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1584","DOI":"10.1212\/WNL.0b013e3182900380","article-title":"Severe congenital RYR1-associated myopathy: the expanding clinicopathologic and genetic spectrum","volume":"80","author":"Bharucha-Goebel","year":"2013","journal-title":"Neurology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1212\/WNL.55.11.1689","article-title":"A novel ryanodine receptor gene mutation causing both cores and rods in congenital myopathy","volume":"55","author":"Scacheri","year":"2000","journal-title":"Neurology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1001\/archneur.61.1.27","article-title":"Multiminicore myopathy, central core disease, malignant hyperthermia susceptibility, and RYR1 mutations: one disease with many faces?","volume":"61","author":"Mathews","year":"2004","journal-title":"Arch Neurol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1186\/1750-1172-2-31","article-title":"Multi-minicore disease","volume":"2","author":"Jungbluth","year":"2007","journal-title":"Orphanet J Rare Dis"},{"key":"B11","doi-asserted-by":"publisher","first-page":"E1544","DOI":"10.1002\/humu.21278","article-title":"Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion","volume":"31","author":"Clarke","year":"2010","journal-title":"Hum Mutat"},{"key":"B12","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1002\/ana.22119","article-title":"RYR1 mutations are a common cause of congenital myopathies with central nuclei","volume":"68","author":"Wilmshurst","year":"2010","journal-title":"Ann Neurol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/ane.12885","article-title":"Phenotype and genotype of muscle ryanodine receptor rhabdomyolysis-myalgia syndrome","author":"Witting","year":"2017","journal-title":"Acta Neurol Scand"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e412","DOI":"10.1212\/WNL.0000000000004894","article-title":"Atypical periodic paralysis and myalgia. A novel RYR1phenotype","volume":"90","author":"Matthews","year":"2018","journal-title":"Neurology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.1093\/brain\/awl077","article-title":"Central core disease is due to RYR1 mutations in more than 90% of patients","volume":"129","author":"Wu","year":"2006","journal-title":"Brain"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2341","DOI":"10.1093\/brain\/awg244","article-title":"Dominant and recessive central core disease associated with RYR1 mutations and fetal akinesia","volume":"126","author":"Romero","year":"2003","journal-title":"Brain"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.1038\/ejhg.2011.179","article-title":"Clinical utility gene card for: central core disease","volume":"20","author":"Lillis","year":"2012","journal-title":"Eur J Hum Genet"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1213\/ane.0b013e3181ac1548","article-title":"Prevalence of malignant hyperthermia due to anesthesia in New York State, 2001-2005","volume":"109","author":"Brady","year":"2009","journal-title":"Anesth Analg"},{"key":"B19","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/s13023-015-0310-1","article-title":"Malignant hyperthermia: a review","volume":"10","author":"Rosenberg","year":"2015","journal-title":"Orphanet J Rare Dis"},{"key":"B20","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1002\/(SICI)1098-1004(200005)15:5<410::AID-HUMU2>3.0.CO;2-D","article-title":"Ryanodine receptor mutations in malignant hyperthermia and central core disease","volume":"15","author":"McCarthy","year":"2000","journal-title":"Hum Mutat"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.1212\/CON.0000000000000404","article-title":"An overview of congenital myopathies","volume":"22","author":"Mah","year":"2016","journal-title":"Continuum (Minneap Minn)"},{"key":"B22","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1002\/ana.21089","article-title":"C-terminal titin deletions cause a novel early-onset myopathy with fatal cardiomyopathy","volume":"61","author":"Carmignac","year":"2007","journal-title":"Ann Neurol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s10048-012-0315-z","article-title":"Mutations in the satellite cell gene MEGF10 cause a recessive congenital myopathy with minicores","volume":"13","author":"Boyden","year":"2012","journal-title":"Neurogenetics"},{"key":"B24","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/1750-1172-3-26","article-title":"Centronuclear (myotubular) myopathy","volume":"3","author":"Jungbluth","year":"2008","journal-title":"Orphanet J Rare Dis"},{"key":"B25","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.spen.2011.10.008","article-title":"Congenital fiber-type disproportion","volume":"18","author":"Clarke","year":"2011","journal-title":"Semin Pediatr Neurol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"e31","DOI":"10.1111\/j.1468-1331.2008.02094.x","article-title":"Novel RYR1 missense mutation causes core rod myopathy","volume":"15","author":"von der Hagen","year":"2008","journal-title":"Eur J Neurol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1212\/WNL.0b013e3181bacf45","article-title":"Core-rod myopathy caused by mutations in the nebulin gene","volume":"73","author":"Romero","year":"2009","journal-title":"Neurology"},{"key":"B28","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.nmd.2013.11.003","article-title":"Approach to the diagnosis of congenital myopathies","volume":"24","author":"North","year":"2014","journal-title":"Neuromuscul Disord"},{"key":"B29","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1183\/09031936.05.00034505","article-title":"General considerations for lung function testing","volume":"26","author":"Miller","year":"2005","journal-title":"Eur Respir J"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1183\/09031936.00080312","article-title":"Multi-ethnic reference values for spirometry for the 3\u201395 year age range: the global lung function 2012 equations: report of the global lung function initiative (GLI), ERS task force to establish improved lung function reference values","volume":"40","author":"Quanjer","year":"2012","journal-title":"Eur Respir J"},{"key":"B32","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1136\/pn.2008.152611","article-title":"Neuromuscular disease and respiratory failure","volume":"8","author":"Hutchinson","year":"2008","journal-title":"Pract Neurol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1177\/0883073810381924","article-title":"Consensus statement on standard of care for congenital muscular dystrophies","volume":"25","author":"Wang","year":"2010","journal-title":"J Child Neurol"},{"key":"B34","first-page":"79","article-title":"Neuromuscular disorders in clinical practice","volume-title":"Neuromuscular Disorders in Clinical Practice","author":"Ruff","year":"2014"},{"key":"B35","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/j.pmr.2012.06.011","article-title":"Clinical approach to the diagnostic evaluation of hereditary and acquired neuromuscular diseases","volume":"23","author":"McDonald","year":"2012","journal-title":"Phys Med Rehabil Clin N Am"},{"key":"B36","doi-asserted-by":"publisher","first-page":"145.e","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"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.1085\/jgp.201711878","article-title":"The structural basis of ryanodine receptor ion channel function","author":"Meissner","year":"2017","journal-title":"J Gen Physiol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1016\/j.nmd.2004.08.005","article-title":"Magnetic resonance imaging of muscle in congenital myopathies associated with RYR1 mutations","volume":"14","author":"Jungbluth","year":"2004","journal-title":"Neuromuscul Disord"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1001\/archneurol.2011.188","article-title":"Muscle magnetic resonance imaging in congenital myopathies due to ryanodine receptor type 1 gene mutations","volume":"68","author":"Klein","year":"2011","journal-title":"Arch Neurol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1097\/FPC.0000000000000198","article-title":"PharmGKB summary: very important pharmacogene information for RYR1","volume":"26","author":"Alvarellos","year":"2016","journal-title":"Pharmacogenet Genomics"},{"key":"B41","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1038\/jhg.2016.2","article-title":"New massive parallel sequencing approach improves the genetic characterization of congenital myopathies","volume":"61","author":"Oliveira","year":"2016","journal-title":"J Hum Genet"},{"key":"B42","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1212\/01.wnl.0000269792.63927.86","article-title":"Congenital neuromuscular disease with uniform type 1 fiber and RYR1 mutation","volume":"70","author":"Sato","year":"2008","journal-title":"Neurology"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1007\/s00415-012-6817-7","article-title":"A novel late-onset axial myopathy associated with mutations in the skeletal muscle ryanodine receptor (RYR1) gene","volume":"260","author":"Loseth","year":"2013","journal-title":"J Neurol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1002\/humu.20356","article-title":"Mutations in RYR1 in malignant hyperthermia and central core disease","volume":"27","author":"Robinson","year":"2006","journal-title":"Hum Mutat"},{"key":"B45","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1016\/j.molmed.2012.09.006","article-title":"Mapping domains and mutations on the skeletal muscle ryanodine receptor channel","volume":"18","author":"Hwang","year":"2012","journal-title":"Trends Mol Med"},{"key":"B46","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1093\/bja\/aew065","article-title":"Comparison of pathogenicity prediction tools on missense variants in RYR1 and CACNA1S associated with malignant hyperthermia","volume":"117","author":"Schiemann","year":"2016","journal-title":"Br J Anaesth"},{"key":"B47","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1086\/301748","article-title":"Identification of novel mutations in the ryanodine-receptor gene (RYR1) in malignant hyperthermia: genotype-phenotype correlation","volume":"62","author":"Manning","year":"1998","journal-title":"Am J Hum Genet"},{"key":"B48","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/BF00690806","article-title":"Coexistence of minicores, cores, and rods in the same muscle biopsy. A new example of mixed congenital myopathy","volume":"58","author":"Vallat","year":"1982","journal-title":"Acta Neuropathol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.spen.2011.10.005","article-title":"Core myopathies","volume":"18","author":"Jungbluth","year":"2011","journal-title":"Semin Pediatr Neurol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/S0960-8966(98)00043-1","article-title":"Fifty year follow-up of a patient with central core disease shows slow but definite progression","volume":"8","author":"Lamont","year":"1998","journal-title":"Neuromuscul Disord"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e33","DOI":"10.1136\/jmg.2003.014274","article-title":"RYR1 mutations in UK central core disease patients: more than just the C-terminal transmembrane region of the RYR1 gene","volume":"41","author":"Shepherd","year":"2004","journal-title":"J Med Genet"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1202","DOI":"10.1007\/s12630-017-0978-x","article-title":"Idiopathic hyperCKemia and malignant hyperthermia susceptibility","volume":"64","author":"Santos","year":"2017","journal-title":"Can J Anaesth"},{"key":"B53","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1136\/adc.88.12.1051","article-title":"Central core disease: clinical, pathological, and genetic features","volume":"88","author":"Quinlivan","year":"2003","journal-title":"Arch Dis Child"},{"key":"B54","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1177\/08830738060210021301","article-title":"Central core disease: atypical case with respiratory insufficiency in an intensive care unit","volume":"21","author":"Polat","year":"2006","journal-title":"J Child Neurol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1001\/jamaneurol.2017.3339","article-title":"Association between decline in slow vital capacity and respiratory insufficiency, use of assisted ventilation, tracheostomy, or death in patients with amyotrophic lateral sclerosis","volume":"75","author":"Andrews","year":"2018","journal-title":"JAMA Neurol"},{"key":"B56","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1002\/9781119973331.ch14","article-title":"Congenital myopathies","volume-title":"Neuromuscular Disorders","author":"Clarke","year":"2011"},{"key":"B57","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1007\/s00401-012-0982-8","article-title":"Next generation sequencing for molecular diagnosis of neuromuscular diseases","volume":"124","author":"Vasli","year":"2012","journal-title":"Acta Neuropathol"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fneur.2018.00118\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,3,5]],"date-time":"2018-03-05T02:47:45Z","timestamp":1520218065000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fneur.2018.00118\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,3,5]]},"references-count":57,"alternative-id":["10.3389\/fneur.2018.00118"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2018.00118","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,3,5]]},"article-number":"118"}}