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Title: Functional characterization of 2 known ryanodine receptor mutations causing malignant hyperthermia.
Authors: Schiemann, Anja H
Paul, Neeti
Parker, Remai
Pollock, N 
Bulger, TF
Stowell, Kathryn M
Issue Date: Feb-2014
Source: Anesthesia and analgesia 2014-02; 118(2): 375-80
Abstract: Malignant hyperthermia (MH) is a potentially lethal pharmacogenetic disorder. More than 300 variants in the ryanodine receptor 1 (RYR1) have been associated with MH; however, only 31 have been identified as causative. To confirm a mutation in RYR1 as being causative for MH, segregation of the potential mutation in at least 2 unrelated families with MH susceptibility must be demonstrated and functional assays must show abnormal calcium release compared with wild-type RYR1. We used "Hot-spot" DNA screening to identify mutations in RYR1 in 3 New Zealand families. B-lymphoblastoid cells were used to compare the amount of calcium released on stimulation with 4-chloro-m-cresol between wild-type RYR1 cells and cells carrying the new variants in RYR1. We identified a known RYR1 mutation (R2355W) in 2 families and another more recently identified (V2354M) mutation in another family. Both mutations segregated with MH susceptibility in the respective families. Cell lines carrying a mutation in RYR1 showed increased sensitivity to 4-chloro-m-cresol. We propose that R2355W is confirmed as being an MH-causative mutation and suggest that V2354M is a RYR1 mutation likely to cause MH.
DOI: 10.1213/ANE.0b013e3182a273ea
PubMed URL:
Journal Title: Anesthesia and analgesia
Type: Journal Article
Research Support, Non-U.S. Gov't
Appears in Collections:Scholarly and Clinical

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