Screening for Mutations in the RYR1 Gene in Families with Malignant Hyperthermia

2003 ◽  
Vol 21 (1) ◽  
pp. 35-42 ◽  
Author(s):  
Viviane P. Muniz ◽  
Helga C. A. Silva ◽  
Ana Maria C. Tsanaclis ◽  
Mariz Vainzof
Keyword(s):  
Malignant Hyperthermia ◽  
Ryr1 Gene

scholarly journals Malignant hyperthermia-a large kindred linked to the RYR1 gene

Anaesthesia ◽  
1996 ◽  
Vol 51 (1) ◽  
pp. 16-23 ◽  
Author(s):  
A. J. WALLACE ◽  
W. WOOLDRIDGE ◽  
H. M. KINGSTON ◽  
M. J. HARRISON ◽  
F. R. ELLIS ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryr1 Gene

Results of Contracture Tests with Halothane, Caffeine, and Ryanodine Depend on Different Malignant Hyperthermia-associated Ryanodine Receptor Gene Mutations

2002 ◽  
Vol 97 (2) ◽  
pp. 345-350 ◽  
Author(s):  
Marko Fiege ◽  
Frank Wappler ◽  
Ralf Weisshorn ◽  
Mark Ulrich Gerbershagen ◽  
Markus Steinfath ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Time Course ◽  
Clinical Symptoms ◽  
Receptor Gene ◽  
Gene Mutations ◽  
Onset Time ◽  
Release Channel ◽  
Ryr1 Gene

Background More than 20 mutations in the gene encoding for the ryanodine receptor (RYR1), a Ca2+ release channel of the skeletal muscle sarcoplasmic reticulum, have been found to be associated with malignant hyperthermia (MH). This study was designed to investigate the effects of different mutations in the RYR1 gene on contracture development in in vitro contracture tests (IVCT) with halothane, caffeine, and ryanodine. Methods Ninety-three MH-susceptible (MHS) patients, diagnosed by the standard IVCT with halothane and caffeine, were included in this prospective study. Surplus muscle specimens were used for an IVCT with 1 microm ryanodine. The contracture course during the ryanodine IVCT was described by the attainment of different time points: onset time of contracture and times when contracture reached 2 mN or 10 mN. In addition, all patients were screened for mutations of the RYR1 gene. Results In 36 patients, four different mutations of the RYR1 gene (C487-T, G1021-A, C1840-T, G7300-A) were found. The IVCT threshold concentrations of halothane and caffeine were lower in patients with the C487-T mutation compared with patients without a detected mutation in the RYR1 gene. In the IVCT with ryanodine, contracture levels of 2 mN and 10 mN were reached earlier in muscle specimens from patients with C487-T, C1840-T, and G7300-A mutations compared with specimens from patients with the G1021-A mutation and patients without detected mutation in the RYR1 gene. Conclusions The differences between the groups in the halothane and caffeine IVCT threshold concentrations and in the time course of contracture development in the ryanodine IVCT underline the hypothesis that certain mutations in the RYR1 gene could make the ryanodine receptor more sensitive to specific ligands. This may be an explanation for varying clinical symptoms of MH crisis in humans.

scholarly journals Exertional Heat Stroke and Susceptibility to Malignant Hyperthermia in an Athlete: Evidence for a Link?

2015 ◽  
Vol 50 (11) ◽  
pp. 1212-1214 ◽  
Author(s):  
Mathias Poussel ◽  
Philippe Guerci ◽  
Pierre Kaminsky ◽  
Marie Heymonet ◽  
Nathalie Roux-Buisson ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Oxidative Metabolism ◽  
Heat Stroke ◽  
Return To Sport ◽  
Fresh Frozen Plasma ◽  
Multiple Organ ◽  
Exertional Heat Stroke ◽  
Ryr1 Gene ◽  
Missense Variation ◽  
Fresh Frozen

Objective  To describe the possible association (pathophysiologic and clinical features) between exertional heat stroke (EHS) and malignant hyperthermia (MH). Background  Both EHS and MH are acute and life-threatening disorders. It has repeatedly been shown that EHS can occur in well-trained patients with known MH-associated mutation in the RYR1 gene in the absence of any extreme environmental conditions or extreme physical activity, thereby supporting a possible link between EHS and MH. In this case, a highly trained 30-year-old male athlete suddenly collapsed while running. He had initial hyperthermia (40.2°C) and progressive multiple organ failure requiring medical management in an intensive care unit. After he recovered completely, a maximal exercise test was performed and showed an obvious abnormality of oxidative metabolism in muscle; genetic analysis of the RYR1 gene identified a heterozygous missense variation p.K1393R. Consequently, the athlete was given appropriate information and allowed to progressively return to sport competition. Differential Diagnosis  Doping, use of drugs and toxic agents, exercise-associated hyponatremia, exertional heat illness. Treatment  Initial management started with the basic resuscitative guidelines of airway, breathing, and circulation (intubation). Cooling, administration of fresh frozen plasma, and intensive rehydration resulted in improvement. Uniqueness  To our knowledge, ours is the first description of this MH mutation (p.K1393R) in the RYR1 gene that was associated with exertional rhabdomyolysis involving a dramatic impairment of oxidative metabolism in muscle. Conclusions  Common features are shared by EHS and MH. Careful attention must therefore be paid to athletes who experience EHS, especially in temperate climates or when there are no other predisposing factors.

scholarly journals Scanning for Mutations of the Ryanodine Receptor (RYR1) Gene by Denaturing HPLC: Detection of Three Novel Malignant Hyperthermia Alleles

2003 ◽  
Vol 49 (5) ◽  
pp. 761-768 ◽  
Author(s):  
Angela Tammaro ◽  
Adele Bracco ◽  
Santolo Cozzolino ◽  
Maria Esposito ◽  
Antonietta Di Martino ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Sudden Increase ◽  
Gene Encoding ◽  
In Vitro Contracture Test ◽  
Ryr1 Gene ◽  
Molecular Tests ◽  
Anesthetic Agents

Abstract Background: Malignant hyperthermia (MH) is a fatal autosomal dominant pharmacogenetic disorder characterized by skeletal muscle hypertonicity that causes a sudden increase in body temperature after exposure to common anesthetic agents. The disease is genetically heterogeneous, with mutations in the gene encoding the skeletal muscle ryanodine receptor (RYR1) at 19q13.1 accounting for up to 80% of the cases. To date, at least 42 RYR1 mutations have been described that cause MH and/or central core disease. Because the RYR1 gene is huge, containing 106 exons, molecular tests have focused on the regions that are more frequently mutated. Thus the causative defect has been identified in only a fraction of families as linked to chromosome 19q, whereas in others it remains undetected. Methods: We used denaturing HPLC (DHPLC) to analyze the RYR1 gene. We set up conditions to scan the 27 exons to identify both known and unknown mutations in critical regions of the protein. For each exon, we analyzed members from 52 families with positive in vitro contracture test results, but without preliminary selection by linkage analysis. Results: We identified seven different mutations in 11 MH families. Among them, three were novel MH alleles: Arg44Cys, Arg533Cys, and Val2117Leu. Conclusion: Because of its sensitivity and speed, DHPLC could be the method of choice for the detection of unknown mutations in the RYR1 gene.

Novel missense mutations and unexpected multiple changes of RYR1 gene in 75 malignant hyperthermia families

2011 ◽  
Vol 79 (5) ◽  
pp. 438-447 ◽  
Author(s):  
A Tammaro ◽  
A Di Martino ◽  
A Bracco ◽  
S Cozzolino ◽  
G Savoia ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Missense Mutations ◽  
Ryr1 Gene

A search for three known RYR1 gene mutations in 41 Swedish families with predisposition to malignant hyperthermia

2008 ◽  
Vol 48 (1) ◽  
pp. 12-16 ◽  
Author(s):  
T. H. Fagerlund ◽  
G. Islander ◽  
E. R. Twetman ◽  
K. Berg
Keyword(s):  
Malignant Hyperthermia ◽  
Gene Mutations ◽  
Ryr1 Gene

Polymorphisms and deduced amino acid substitutions in the coding sequence of the ryanodine receptor (RYR1) gene in individuals with malignant hyperthermia

Genomics ◽  
1992 ◽  
Vol 13 (4) ◽  
pp. 1247-1254 ◽  
Author(s):  
Elizabeth F. Gillard ◽  
Kinya Otsu ◽  
Junichi Fujii ◽  
Catherine Duff ◽  
Stella de Leon ◽  
...  
Keyword(s):  
Amino Acid ◽  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Amino Acid Substitutions ◽  
Coding Sequence ◽  
Ryr1 Gene

Search for three known mutations in the RYR1 gene in 48 Danish families with malignant hyperthermia

2008 ◽  
Vol 46 (6) ◽  
pp. 401-404 ◽  
Author(s):  
T. Fagerlund ◽  
H. Ørding ◽  
D. Bendixen ◽  
K. Berg
Keyword(s):  
Malignant Hyperthermia ◽  
Ryr1 Gene
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