{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:18:34Z","timestamp":1790619514217,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["2021\/06180-7"],"award-info":[{"award-number":["2021\/06180-7"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","award":["2013\/8028-1"],"award-info":[{"award-number":["2013\/8028-1"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de 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Paulo\u2014Centro de Pesquisa, Inova\u00e7\u00e3o e Difus\u00e3o","award":["2013\/8028-1"],"award-info":[{"award-number":["2013\/8028-1"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo\u2014Centro de Pesquisa, Inova\u00e7\u00e3o e Difus\u00e3o","award":["465355\/2014-5"],"award-info":[{"award-number":["465355\/2014-5"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u0131fico e Tecnol\u00f3gico","award":["2021\/06180-7"],"award-info":[{"award-number":["2021\/06180-7"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u0131fico e Tecnol\u00f3gico","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u0131fico e Tecnol\u00f3gico","award":["2013\/8028-1"],"award-info":[{"award-number":["2013\/8028-1"]}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u0131fico e Tecnol\u00f3gico","award":["465355\/2014-5"],"award-info":[{"award-number":["465355\/2014-5"]}]},{"name":"Financiadora de Estudos e Projetos (FINEP)","award":["2021\/06180-7"],"award-info":[{"award-number":["2021\/06180-7"]}]},{"name":"Financiadora de Estudos e Projetos (FINEP)","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"Financiadora de Estudos e Projetos (FINEP)","award":["2013\/8028-1"],"award-info":[{"award-number":["2013\/8028-1"]}]},{"name":"Financiadora de Estudos e Projetos (FINEP)","award":["465355\/2014-5"],"award-info":[{"award-number":["465355\/2014-5"]}]},{"name":"CAPES\u2014Coordena\u00e7\u00e3o de aperfei\u00e7oamento de Pessoal de Nivel Superior","award":["2021\/06180-7"],"award-info":[{"award-number":["2021\/06180-7"]}]},{"name":"CAPES\u2014Coordena\u00e7\u00e3o de aperfei\u00e7oamento de Pessoal de Nivel Superior","award":["001"],"award-info":[{"award-number":["001"]}]},{"name":"CAPES\u2014Coordena\u00e7\u00e3o de aperfei\u00e7oamento de Pessoal de Nivel Superior","award":["2013\/8028-1"],"award-info":[{"award-number":["2013\/8028-1"]}]},{"name":"CAPES\u2014Coordena\u00e7\u00e3o de aperfei\u00e7oamento de Pessoal de Nivel Superior","award":["465355\/2014-5"],"award-info":[{"award-number":["465355\/2014-5"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Malignant hyperthermia (MH) is a pharmacogenetic hypermetabolic syndrome triggered by halogenated agents\/succinylcholine. Most families present variants in the RYR1 and, rarely, in other genes (CACNA1S\/STAC3\/ASPH). However, each country or region presents differences in the type and frequency of MH variants. Objective: To present the genetic characteristics of Brazilian individuals with MH history. Methods: We reviewed clinical and laboratory data from all families referred for evaluation in the Brazilian MH unit due to a personal or family history of MH during anesthesia. Demographic and clinical data were collected, as well as serum creatine kinase (CK) levels, in vitro contracture test (IVCT) results, and the results of anatomopathological studies of skeletal muscle. Molecular analysis was performed using whole-exome sequencing (WES). Patients with and without variants were compared. Results: WES analysis was available for 61 patients (29 patients who survived an MH crisis and 32 relatives). Variants in the RYR1 were found in 38 patients (62.2%), and no variants were identified in 20 patients (32.7%). More than one variant in the RYR1 was found in six individuals. Variants in the CACNA1S were found in three patients (4.9%), all of them with concomitant variants in the RYR1. Three patients presented variants in the STAC3 (4.9%). Comparing the groups of patients with variants in the RYR1 with the one with no variants in this gene, it was observed that the first group showed higher levels of serum CK, a greater frequency of ptosis, strabismus, and cores, and a higher amplitude of contracture in the IVCT after caffeine or halothane. Conclusion: In this preliminary evaluation of Brazilian individuals with MH history, the frequency of RYR1 variants was similar to those of previous reports in other countries, but there was a higher frequency of STAC3 and CACNA1S variants.<\/jats:p>","DOI":"10.3390\/genes16101127","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T08:56:44Z","timestamp":1758790604000},"page":"1127","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic Characteristics of Brazilian Patients with MH History"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9372-7019","authenticated-orcid":false,"given":"Helga C. A.","family":"Silva","sequence":"first","affiliation":[{"name":"Brazilian Malignant Hyperthermia Unit, Department of Anesthesiology, Pain and Intensive Care, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 04039-032, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela C.","family":"Mendon\u00e7a","sequence":"additional","affiliation":[{"name":"Brazilian Malignant Hyperthermia Unit, Department of Anesthesiology, Pain and Intensive Care, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 04039-032, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7066-262X","authenticated-orcid":false,"given":"Brandow W.","family":"Souza","sequence":"additional","affiliation":[{"name":"Human Genome and Stem Cells Research Center, Institute of Biosciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-090, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joilson M.","family":"Santos","sequence":"additional","affiliation":[{"name":"Brazilian Malignant Hyperthermia Unit, Department of Anesthesiology, Pain and Intensive Care, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 04039-032, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas S.","family":"Souza","sequence":"additional","affiliation":[{"name":"Human Genome and Stem Cells Research Center, Institute of Biosciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-090, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio F. R.","family":"Junior","sequence":"additional","affiliation":[{"name":"Human Genome and Stem Cells Research Center, Institute of Biosciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-090, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe T. G. R.","family":"Vasconcelos","sequence":"additional","affiliation":[{"name":"Human Genome and Stem Cells Research Center, Institute of Biosciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-090, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela V.","family":"Andrade","sequence":"additional","affiliation":[{"name":"Brazilian Malignant Hyperthermia Unit, Department of Anesthesiology, Pain and Intensive Care, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 04039-032, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6986-4937","authenticated-orcid":false,"given":"Acary S. B.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Neurology, Federal University of S\u00e3o Paulo, S\u00e3o Paulo 040039-032, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2797-0782","authenticated-orcid":false,"given":"Mariz","family":"Vainzof","sequence":"additional","affiliation":[{"name":"Human Genome and Stem Cells Research Center, Institute of Biosciences, University of S\u00e3o Paulo, S\u00e3o Paulo 05508-090, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"ref_1","unstructured":"Adam, M.P., Feldman, J., Mirzaa, G.M., Pagon, R.A., Wallace, S.E., and Amemiya, A. (2025, July 31). 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Biol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/10\/1127\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:49:24Z","timestamp":1760035764000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/10\/1127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,25]]},"references-count":30,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["genes16101127"],"URL":"https:\/\/doi.org\/10.3390\/genes16101127","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,25]]}}}