{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:24:39Z","timestamp":1760783079315,"version":"build-2065373602"},"reference-count":32,"publisher":"BMJ","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1997,4]]},"abstract":"<jats:p>Defects in the ryanodine receptor (RYR1) gene are associated with malignant hyperthermia (MH), an autosomal dominant disorder of skeletal muscle and one of the main causes of death resulting from anaesthesia. Susceptibility to MH (MHS) is determined by the level of tension generated in an in vitro muscle contracture test (IVCT) in response to caffeine and halothane. To date, mutation screening of the RYR1 gene in MH families has led to the identification of eight mutations. We describe here the identification of a novel mutation, Arg552Trp, in the RYR1 gene, which is clearly linked to the MHS phenotype in a large, well characterised Irish pedigree. Considering that the RYR1 protein functions as a tetramer, correlation of the IVCT with the affected and unaffected haplotypes was performed on the pedigree to investigate if the normal RYR1 allele in affected subjects contributes to the variation in the IVCT. The results show that the normal RYR1 allele is unlikely to play a role in IVCT variation.<\/jats:p>","DOI":"10.1136\/jmg.34.4.291","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"291-296","source":"Crossref","is-referenced-by-count":30,"title":["Detection of a novel mutation in the ryanodine receptor gene in an Irish malignant hyperthermia pedigree: correlation of the IVCT response with the affected and unaffected haplotypes."],"prefix":"10.1136","volume":"34","author":[{"given":"K E","family":"Keating","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L","family":"Giblin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P J","family":"Lynch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K A","family":"Quane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Lehane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J J","family":"Heffron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T V","family":"McCarthy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1997,4,1]]},"reference":[{"key":"ref_1","first-page":"325","article-title":"Dantrolene-an update","author":"Britt, B.A.","year":"1987","unstructured":"Britt BA. 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Hunt Mol Geniet 1994;3:471-6.","journal-title":"Hunt Mol Geniet"},{"key":"ref_14","first-page":"236","article-title":"Mutation screening of the RYRI gene in malignant hyperthermia: detection of a novel Tyr to Ser mutation in a pedigree with associated central cores","volume":"23","author":"Quane, K.A.; Keating, K.E.; Healy, J.M.S.; ct al","year":"1994","unstructured":"Quane KA, Keating KE, Healy JMS, ct al. Mutation screening of the RYRI gene in malignant hyperthermia: detection of a novel Tyr to Ser mutation in a pedigree with associated central cores. Genomsnics 1994;23:236-9.","journal-title":"Genomsnics"},{"key":"ref_15","first-page":"751","article-title":"A substitution of cvsteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia","volume":"11","author":"Gillard, E.F.; Ostu, K.; Fujii, J.","year":"1991","unstructured":"Gillard EF, Ostu K, Fujii J, et al. A substitution of cvsteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia. Getttsnttcs 1991;11:751-5.","journal-title":"Getttsnttcs"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1855","DOI":"10.1093\/hmg\/3.10.1855","article-title":"Detection of a novel RYRI mutation in four malignant hyperthermia pedigrees","volume":"3","author":"Keating, K.E.; Quane, K.A.; Manning, B.M.","year":"1994","unstructured":"Keating KE, Quane KA, Manning BM, et al. Detection of a novel RYRI mutation in four malignant hyperthermia pedigrees. Huint Mol Geniet 1994;3:1855-8.","journal-title":"Huint Mol Geniet"},{"key":"ref_17","first-page":"2181","article-title":"The substitution of Arg for Gly 2433 in the human skeletal muscle ryanodine receptor is associated with malignant hyperthermia","volume":"3","author":"Philips, M.S.; Khanna, V.K.; DeLeon, S.; Frodis, W.; Britt, B.A.; MacLennan, D.H.","year":"1994","unstructured":"Philips MS, Khanna VK, DeLeon S, Frodis W, Britt BA, MacLennan DH. The substitution of Arg for Gly 2433 in the human skeletal muscle ryanodine receptor is associated with malignant hyperthermia. Huntl Mtol Gettet 1994;3: 2181-6.","journal-title":"Huntl Mtol Gettet"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/ng0993-46","article-title":"A mutation in the human ryanodine receptor gene associated with central core disease","volume":"5","author":"Zhang, Y.; Chen, H.S.; Khanna, V.K.","year":"1993","unstructured":"Zhang Y, Chen HS, Khanna VK, et al. 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