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Functional characterization of the RYR1 mutation p.Arg4737Trp associated with susceptibility to malignant hyperthermia

Johansen, Stephan and Treves, Susan and Müller, Clemens R. and Mögele, Susanne and Schneiderbanger, Daniel and Roewer, Norbert and Schuster, Frank. (2016) Functional characterization of the RYR1 mutation p.Arg4737Trp associated with susceptibility to malignant hyperthermia. Neuromuscular Disorders, 26 (1). pp. 21-25.

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Abstract

Aside from the in vitro contracture test, genetic screening for causative RYR1 mutations is the established procedure to diagnose susceptibility to malignant hyperthermia (MH). However, currently only 34 out of more than 300 known RYR1 mutations have been confirmed to be causative for MH by experimental studies addressing their functional impact on intracellular calcium homeostasis. The RYR1 mutation p.Arg4737Trp has been recently detected in a German MH family. To evaluate the effects of that mutation on intracellular calcium handling, the response after stimulation with the RYR1 agonist 4-chloro-m-cresol was investigated in immortalized B lymphocytes containing the p.Arg4737Trp mutation and compared to the response of wild type RYR1 from unaffected family members and unrelated controls. Intracellular resting calcium was slightly but significantly elevated in mutation positive cells. Calcium release following stimulation with 4-chloro-m-cresol was significantly increased in B lymphocytes carrying the p.Arg4737Trp mutation compared to mutation negative controls. Hence, the functional properties of the RYR1 mutation p.Arg4737Trp are consistent with susceptibility to MH Together with previously published data, the mutation has now been reported in three independent MH positive families.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Perioperative Patient Safety (Girard/Treves)
UniBasel Contributors:Treves, Susan
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0960-8966
e-ISSN:0960-8966
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:31 May 2017 09:20
Deposited On:18 Oct 2016 12:42

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