Additional evidence that the ryanodine receptor gene (RYR1) causes malignant hyperthermia and severe skeletal malformations

2012 ◽  
Vol 161 (1) ◽  
pp. 234-235
Author(s):  
Yosuke Kakisaka ◽  
Kazuhiro Haginoya ◽  
Yuko Takahashi ◽  
Tatsuhiro Ochiai ◽  
Ikuma Fujiwara ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Receptor Gene ◽  
Skeletal Malformations

scholarly journals Genetics of Malignant Hyperthermia

2006 ◽  
Vol 6 ◽  
pp. 1722-1730 ◽  
Author(s):  
Barbara W. Brandom
Keyword(s):  
Malignant Hyperthermia ◽  
Candidate Genes ◽  
Ryanodine Receptor ◽  
Receptor Gene ◽  
Linkage Studies ◽  
Chromosome 19

Study of the genetics of the malignant hyperthermia syndrome began in families in which both malignant hyperthermia (MH) episodes had been experienced and individuals had strongly positive contracture tests diagnostic of susceptibility to MH. Linkage studies associated this MH phenotype to the ryanodine receptor gene (RYR1) at chromosome 19q13.1 in many families. Although the MH phenotype is not always linked to chromosome 19, theRYR1has remained the focus of experimentation. Other candidate genes exist, but few MH-susceptible families have variants of these genes. Hundreds of MH-susceptible people have variants ofRYR1.

Molecular Genetic Analysis of the Ryanodine Receptor Gene (RYR1) in Korean Malignant Hyperthermia Families

2010 ◽  
Vol 30 (6) ◽  
pp. 702-710 ◽  
Author(s):  
Ho Lee ◽  
Dong Chan Kim ◽  
Jae Hyeon Lee ◽  
Yong Gon Cho ◽  
Hye Soo Lee ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Receptor Gene ◽  
Molecular Genetic ◽  
Molecular Genetic Analysis

scholarly journals Functional properties of ryanodine receptors carrying three amino acid substitutions identified in patients affected by multi-minicore disease and central core disease, expressed in immortalized lymphocytes

2006 ◽  
Vol 395 (2) ◽  
pp. 259-266 ◽  
Author(s):  
Sylvie Ducreux ◽  
Francesco Zorzato ◽  
Ana Ferreiro ◽  
Heinz Jungbluth ◽  
Francesco Muntoni ◽  
...  
Keyword(s):  
Amino Acid ◽  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Receptor Gene ◽  
Receptor Activation ◽  
Central Core ◽  
Central Core Disease ◽  
Amino Acid Substitutions ◽  
Time Data ◽  
Minicore Disease

More than 80 mutations in the skeletal muscle ryanodine receptor gene have been found to be associated with autosomal dominant forms of malignant hyperthermia and central core disease, and with recessive forms of multi-minicore disease. Studies on the functional effects of pathogenic dominant mutations have shown that they mostly affect intracellular Ca2+ homoeostasis, either by rendering the channel hypersensitive to activation (malignant hyperthermia) or by altering the amount of Ca2+ released subsequent to physiological or pharmacological activation (central core disease). In the present paper, we show, for the first time, data on the functional effect of two recently identified recessive ryanodine receptor 1 amino acid substitutions, P3527S and V4849I, as well as that of R999H, another substitution that was identified in two siblings that were affected by multi-minicore disease. We studied the intracellular Ca2+ homoeostasis of EBV (Epstein–Barr virus)-transformed lymphoblastoid cells from the affected patients, their healthy relatives and control individuals. Our results show that the P3527S substitution in the homozygous state affected the amount of Ca2+ released after pharmacological activation with 4-chloro-m-cresol and caffeine, but did not affect the size of the thapsigargin-sensitive Ca2+ stores. The other substitutions had no effect on either the size of the intracellular Ca2+ stores, or on the amount of Ca2+ released after ryanodine receptor activation; however, both the P3527S and V4849I substitutions had a small but significant effect on the resting Ca2+ concentration.

A Fulminant Malignant Hyperthermia Episode in a Patient with Ryanodine Receptor Gene Mutation p.Tyr522Ser

2008 ◽  
Vol 107 (6) ◽  
pp. 1953-1955 ◽  
Author(s):  
Thierry Girard ◽  
Markus Suhner ◽  
Soledad Levano ◽  
Martine Singer ◽  
Andreas Zollinger ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Gene Mutation ◽  
Ryanodine Receptor ◽  
Receptor 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.

Ryanodine receptor gene is a candidate for predisposition to malignant hyperthermia

Nature ◽  
1990 ◽  
Vol 343 (6258) ◽  
pp. 559-561 ◽  
Author(s):  
David H. MacLennan ◽  
Catherine Duff ◽  
Francesco Zorzato ◽  
Junichi Fujii ◽  
Michael Phillips ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Receptor Gene

Mutations in the ryanodine receptor gene in central core disease and malignant hyperthermia

1993 ◽  
Vol 5 (1) ◽  
pp. 51-55 ◽  
Author(s):  
K. A. Quane ◽  
J.M.S. Healy ◽  
K. E. Keating ◽  
B. M. Manning ◽  
F. J. Couch ◽  
...  
Keyword(s):  
Malignant Hyperthermia ◽  
Ryanodine Receptor ◽  
Receptor Gene ◽  
Central Core ◽  
Central Core Disease
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