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WES revealed the compound heterozygous mutations, p.Ile235Asn and p.Glu982Lys, in <jats:styled-content style=\"fixed-case\"><jats:italic>ATP2A1<\/jats:italic><\/jats:styled-content>, encoding the sarco(endo)plasmic reticulum Ca<jats:sup>2+<\/jats:sup> ATPase type 1 (<jats:styled-content style=\"fixed-case\">SERCA<\/jats:styled-content>1), a calcium pump, expressed in fast\u2010twitch muscles. Recessive mutations in <jats:styled-content style=\"fixed-case\"><jats:italic>ATP2A1<\/jats:italic><\/jats:styled-content> are known to cause Brody myopathy, a rare muscle disorder characterized by exercise\u2010induced impairment of muscle relaxation and stiffness. Analyses of affected muscles showed the absence of <jats:styled-content style=\"fixed-case\">SERCA<\/jats:styled-content>1, but <jats:styled-content style=\"fixed-case\">SERCA<\/jats:styled-content>2 upregulation in slow and fast myofibers, suggesting a compensatory mechanism that partially restores the diminished Ca<jats:sup>2+<\/jats:sup> transport in Brody myopathy. This compensatory adaptation to the lack of <jats:styled-content style=\"fixed-case\">SERCA<\/jats:styled-content>1 Ca<jats:sup>2+<\/jats:sup> pumping activity within the muscle explains, in part, the mild course of disease in our patient. Diagnosis of <jats:styled-content style=\"fixed-case\">MHS<\/jats:styled-content> in this family was secondary to a loss of <jats:styled-content style=\"fixed-case\">SERCA<\/jats:styled-content>1 due to disease\u2010associated mutations. Although there are obvious differences in clinical expression and molecular mechanisms between <jats:styled-content style=\"fixed-case\">MH<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>rody myopathy, a feature common to both conditions is elevated myoplasmic Ca<jats:sup>2+<\/jats:sup> content. Prolonged intracellular Ca<jats:sup>2+<\/jats:sup> elevation is likely to have led to <jats:styled-content style=\"fixed-case\">MHS<\/jats:styled-content> diagnosis in vitro and postoperative MH\u2010like symptoms in Brody patient.<\/jats:p>","DOI":"10.1002\/mgg3.91","type":"journal-article","created":{"date-parts":[[2014,6,6]],"date-time":"2014-06-06T09:40:49Z","timestamp":1402047649000},"page":"472-483","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Exome analysis identifies <scp>B<\/scp>rody myopathy in a family diagnosed with malignant hyperthermia susceptibility"],"prefix":"10.1002","volume":"2","author":[{"given":"Nyamkhishig","family":"Sambuughin","sequence":"first","affiliation":[{"name":"Defense and Veterans Center for Integrated Pain Management Henry M. 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