AIRR - ANZCA Institutional Research Repository
Skip navigation
Please use this identifier to cite or link to this item:
Title: Functional analysis ofRYR1variants linked to malignant hyperthermia.
Authors: Stephens, J 
Schiemann, Anja H
Roesl, Cornelia
Miller, Dorota
Massey, Sean
Pollock, N 
Bulger, T
Stowell, Kathryn
Issue Date: 2016
Source: Temperature (Austin, Tex.) 2016 Apr-Jun; 3(2): 328-339
Journal Title: Temperature (Austin, Tex.)
Abstract: Malignant hyperthermia manifests as a rapid and sustained rise in temperature in response to pharmacological triggering agents, e.g. inhalational anesthetics and the muscle relaxant suxamethonium. Other clinical signs include an increase in end-tidal CO2, increased O2consumption, as well as tachycardia, and if untreated a malignant hyperthermia episode can result in death. The metabolic changes are caused by dysregulation of skeletal muscle Ca2+homeostasis, resulting from a defective ryanodine receptor Ca2+channel, which resides in the sarcoplasmic reticulum and controls the flux of Ca2+ions from intracellular stores to the cytoplasm. Most genetic variants associated with susceptibility to malignant hyperthermia occur in theRYR1gene encoding the ryanodine receptor type 1. While malignant hyperthermia susceptibility can be diagnosed byin vitrocontracture testing of skeletal muscle biopsy tissue, it is advantageous to use DNA testing. Currently only 35 of over 400 potential variants inRYR1have been classed as functionally causative of malignant hyperthermia and thus can be used for DNA diagnostic tests. Here we describe functional analysis of 2RYR1variants (c. 7042_7044delCAG, p.ΔGlu2348 and c.641C>T, p.Thr214Met) that occur in the same malignant hyperthermia susceptible family. The p.Glu2348 deletion, causes hypersensitivity to ryanodine receptor agonists usingin vitroanalysis of cloned humanRYR1cDNA expressed in HEK293T cells, while the Thr214Met substitution, does not appear to significantly alter sensitivity to agonist in the same system. We suggest that the c. 7042_7044delCAG, p.ΔGlu2348RYR1variant could be added to the list of diagnostic mutations for susceptibility to malignant hyperthermia.
DOI: 10.1080/23328940.2016.1153360
PubMed URL:
ISSN: 2332-8940
Type: Journal Article
Appears in Collections:Scholarly and Clinical

Show full item record

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.