Functional characterization of RYR1 variants identified in malignant hyperthermia susceptible individuals.
Calcium dysregulation
Diagnosis
Malignant hyperthermia
Mutations
Ryanodine receptor
Journal
Neuromuscular disorders : NMD
ISSN: 1873-2364
Titre abrégé: Neuromuscul Disord
Pays: England
ID NLM: 9111470
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
28
06
2023
revised:
25
10
2023
accepted:
30
10
2023
pubmed:
24
11
2023
medline:
24
11
2023
entrez:
23
11
2023
Statut:
ppublish
Résumé
Malignant hyperthermia is a pharmacogenetic disorder triggered by halogenated anesthetic agents in genetically predisposed individuals. Approximately 70 % of these individuals carry mutations in RYR1, the gene encoding the ryanodine receptor calcium channel of skeletal muscle. In this study, we performed functional analysis of 5 RYR1 variants identified in members from 8 families who had been diagnosed by the IVCT. Of the 68 individuals enrolled in the study, 43 were diagnosed as MHS, 23 as MHN, and 2 individuals were not tested. Here we demonstrate that the 5 RyR1 variants cause hypersensitivity to RyR1 agonist-mediated calcium release. According to the EMHG scoring matrix these five genetic variants can be classified as follows: c.8638G>A (p.E2880K) and c.11314C>T (p.R3772W) likely pathogenic, c.11416G>A (p.G3806R), c.14627A>G (p.K4876R) and c.14813T>C (p.I4938T), pathogenic (RefSeq NM_000540.3). We propose that the newly functionally characterized RYR1 variants, be included in the panel of variants to be used for the molecular diagnosis of MHS.
Identifiants
pubmed: 37996280
pii: S0960-8966(23)00772-1
doi: 10.1016/j.nmd.2023.10.019
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
951-963Informations de copyright
Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest All authors declare that they have no conflict of interest.