Multiple interacting gene products may influence susceptibility to malignant hyperthermia

@article{Robinson2000MultipleIG,
  title={Multiple interacting gene products may influence susceptibility to malignant hyperthermia},
  author={Rachel L Robinson and John Curran and F. Richard Ellis and P. Jane Halsall and W. J. Hall and Philip M Hopkins and David E Iles and Sarah West and M‐A. Shaw},
  journal={Annals of Human Genetics},
  year={2000},
  volume={64}
}
Malignant hyperthermia (MH) is a potentially lethal disorder triggered in susceptible individuals on exposure to common anaesthetic agents. Crises reflect the consequences of disturbed skeletal muscle calcium homeostasis. MH is an autosomal dominant, genetically heterogeneous trait. Defects in a single major gene have been assumed to determine susceptibility status in individual families. However, in some pedigrees phenotypic and genotypic data are discordant. One explanation, in contrast to… 
Several interacting genes influence the malignant hyperthermia phenotype
TLDR
Data is presented on a replica analysis of an independent sample of European MH families to support the hypothesis that several genes influence susceptibility in individual families, rather than MH simply being a major gene defect.
Screening for mutations in the RYR1 gene in families with malignant hyperthermia
Malignant hyperthermia (MH) is a potentially lethal pharmacogenetic predisposition associated with a susceptibility to volatile anesthetics and depolarizing muscle relaxants that lead to a fulminant
Epigenetic allele silencing and variable penetrance of malignant hyperthermia susceptibility.
TLDR
Epigenetic allele silencing may play a role in the inheritance of MH susceptibility, but this is unlikely to involve silencing of RYR1.
The role of CACNA1S in predisposition to malignant hyperthermia
TLDR
The study identified a single potentially pathogenic change in CACNA1S (p.Arg174Trp), and highlights that the haplotype structure across CAC NA1S is diverse, with a high degree of variability.
Screening of the Entire Ryanodine Receptor Type 1 Coding Region for Sequence Variants Associated with Malignant Hyperthermia Susceptibility in the North American Population
TLDR
Denaturing high-performance liquid chromatography analysis of RNA samples extracted from the biopsied skeletal muscle followed by DNA sequencing is a highly efficient methodology for RYR1 mutation detection, allowing increasing the rate of mutation detection to 70% and identifying mutations in the entire RYP1 coding region.
Investigating the genetic susceptibility to exertional heat illness
TLDR
A role of RYR1 is confirmed in the heritability of EHI as well as ER but defects, or combinations of defects, in skeletal muscle calcium homeostasis, oxidative metabolism and membrane excitability are associated with EHI.
Recent advances in the diagnosis of malignant hyperthermia susceptibility: How confident can we be of genetic testing?
TLDR
Assessment of RYR1 mutation prevalence and genotype/phenotype correlation analysis in a sample of over 500 unrelated European MH susceptible individuals highlights the possible limitations of MH screening methods.
Malignant hyperthermia
  • Dong-Chan Kim
  • Medicine, Biology
    Korean journal of anesthesiology
  • 2012
TLDR
The mortality of MH is dramatically decreased from 70-80% to less than 5%, due to an introduction of dantrolene sodium for treatment of MH, early detection of MH episode using capnography, and the introduction of diagnostic testing for MHS.
Genetic variation in RYR1 and malignant hyperthermia phenotypes.
TLDR
Differences in phenotype severity between RYR1 variants may explain the variability in clinical penetrance of MH during anaesthesia and why some variants have been associated with exercise-induced rhabdomyolysis and heat stroke.
Current concepts in malignant hyperthermia.
  • J. Finsterer
  • Medicine, Biology
    Journal of clinical neuromuscular disease
  • 2002
TLDR
Consultation by a specialist in MH susceptibility after anesthesia is essential to investigate the patient for MH susceptibility or subclinical myopathy, guide laboratory investigations, manage therapy, and counsel the family on further risk.
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TLDR
Evidence to suggest that at least two further loci exist for MH susceptibility is added, adding to the evidence for considerable genetic heterogeneity in MH and providing a route to further the understanding of the molecular pathology of the condition.
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TLDR
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TLDR
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TLDR
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TLDR
A multipoint analysis excludes the disease from the entire 84 cM interval containing the proposed MHS locus on chromosome 17q, and excludes the alpha 1, beta 1 and gamma subunit of the DHP receptor as well as the SCN4A locus from that region.
Exclusion of malignant hyperthermia susceptibility (MHS) from a putative MHS2 locus on chromosome 17q and of the α1, β1, and γ subunits of the dihydropyridine receptor calcium channel as candidates for the molecular defect
TLDR
A multipoint analysis excludes the disease from the entire 84 cM interval containing the proposed MHS locus on chromosome 17q, and excludes the alpha 1, beta 1 and gamma subunit of the DHP receptor as well as the SCN4A locus from that region.
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TLDR
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