• A R Bjorksten, R L Gillies, B M Hockey, and D Du Sart.
• Senior Scientist, Malignant Hyperthermia Diagnostic Unit, Department of Anaesthesia and Pain Management, Royal Melbourne Hospital, Anaesthesia, Perioperative and Pain Medicine Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Victorian Clinical Genetics Service Molecular Genetics Laboratory, Murdoch Children's Research Institut.
• Anaesth Intensive Care. 2016 Nov 1; 44 (6): 762-768.

AbstractThe genetic basis of malignant hyperthermia (MH) is not fully characterised and likely involves more than just the currently classified mutations in the gene encoding the skeletal muscle ryanodine receptor (RYR1) and the gene encoding the α1 subunit of the dihydropyridine receptor (CACNA1S). In this paper we sequence other genes involved in calcium trafficking within skeletal muscle in patients with positive in vitro contracture tests, searching for alternative genes associated with MH. We identified four rare variants in four different genes (CACNB1, CASQ1, SERCA1 and CASQ2) encoding proteins involved in calcium handling in skeletal muscle in a cohort of 30 Australian MH susceptible probands in whom prior complete sequencing of RYR1 and CACNA1S had yielded no rare variants. These four variants have very low minor allele frequencies and while it is tempting to speculate that they have a role in MH, they remain at present variants of unknown significance. Nevertheless they provide the basis for a new set of functional studies, which may indeed identify novel players in MH.

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