Sequencing of Genes Involved in the Movement of Calcium across Human Skeletal Muscle Sarcoplasmic Reticulum: Continuing the Search for Genes Associated with Malignant Hyperthermia. Issue 6 (November 2016)

• Record Type: Journal Article
• Authors: Bjorksten, A. R.; Gillies, R. L.; Hockey, B. M.; Du Sart, D.
• Is Part Of: Anaesthesia and intensive care. Volume 44:Issue 6(2016)
• Page Start: 762
• Page End: 768
• Publication Date: 2016-11
• Subjects: malignant hyperthermia -- genetic variants; Anesthesiology -- Periodicals; Intensive Care Units -- Periodicals; 617.96
• DOI: 10.1177/0310057X1604400625
• Languages: English
• ISSNs: 0310-057X

Abstract

The 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.