Identification and biochemical characterization of a novel ryanodine receptor gene mutation associated with malignant hyperthermia

Anesthesiology
Ayuk A AndersonKathryn M Stowell

Abstract

Mutations in the skeletal muscle ryanodine receptor gene may result in altered calcium release from sarcoplasmic reticulum stores, giving rise to malignant hyperthermia (MH). MH is a pharmacogenetic skeletal muscle disorder triggered by volatile anesthetics and depolarizing muscle relaxants. Diagnosis of MH is by in vitro contracture testing of quadriceps muscle. DNA analysis of causative mutations is limited by the large number of mutations that cosegregate with MH and the relatively few that have been biochemically characterized. DNA sequence analysis was used to screen the skeletal muscle ryanodine receptor gene in MH-susceptible individuals. A diagnostic test using real-time polymerase chain reaction was developed to detect the mutation in individuals diagnosed as MH susceptible by in vitro contracture testing. The functional relevance of this mutation was examined in Epstein-Barr virus-immortalized B-lymphoblastoid cells. A novel ryanodine receptor mutation (cytosine 14997 thymine resulting in a histidine 4833 tyrosine substitution) was identified in pathology specimens from two patients with fatal MH reactions. B lymphocytes from patients with this mutation were approximately twofold more sensitive than MH-negative cells ...Continue Reading

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Citations

Jun 10, 2011·Regional Anesthesia and Pain Medicine·Marcus BrynolfBjörn Holmström
Sep 11, 2010·Plastic and Reconstructive Surgery·Raffi GurunluogluUNKNOWN ASPS Patient Safety Committee
Nov 21, 2008·Pharmacogenomics·Kathryn M Stowell
Dec 24, 2013·Anesthesia and Analgesia·Anja H SchiemannKathryn M Stowell
Jan 22, 2014·Anesthesia and Analgesia·Kathryn M Stowell
Aug 5, 2015·Orphanet Journal of Rare Diseases·Henry RosenbergKathryn Stowell
Jan 14, 2010·Anesthesiology·Timothy J TautzBruno Riou
Oct 9, 2009·Current Opinion in Anaesthesiology·Barbara W Brandom
Jun 21, 2008·Anaesthesia and Intensive Care·K M Stowell, N Pollock
Apr 14, 2011·Anaesthesia and Intensive Care·M KobayashiO Yuge

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