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Functional characterization of the RYR1 mutation p.Arg4737Trp associated with susceptibility to malignant hyperthermia.
- Source :
-
Neuromuscular disorders : NMD [Neuromuscul Disord] 2016 Jan; Vol. 26 (1), pp. 21-5. Date of Electronic Publication: 2015 Nov 11. - Publication Year :
- 2016
-
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.<br /> (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Subjects :
- Anesthetics pharmacology
B-Lymphocytes drug effects
Caffeine pharmacology
Cell Line, Transformed
Cresols pharmacology
Family Health
Female
Fungicides, Industrial pharmacology
Germany
Halothane pharmacology
Humans
Male
Malignant Hyperthermia pathology
Muscle Contraction drug effects
Muscle Contraction genetics
Muscle, Skeletal drug effects
Muscle, Skeletal physiopathology
Phosphodiesterase Inhibitors pharmacology
Arginine genetics
Genetic Predisposition to Disease genetics
Malignant Hyperthermia genetics
Polymorphism, Single Nucleotide genetics
Ryanodine Receptor Calcium Release Channel genetics
Tryptophan genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2364
- Volume :
- 26
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Neuromuscular disorders : NMD
- Publication Type :
- Academic Journal
- Accession number :
- 26631338
- Full Text :
- https://doi.org/10.1016/j.nmd.2015.11.001