Novel mutations at a CpG dinucleotide in the ryanodine receptor in malignant hyperthermia

Manning, Bernadette M.; Quane, Kathleen A.; Lynch, Patrick J.; Urwyler, Albert; Tegazzin, Vincenzo; Krivosic-Horber, R; Censier, K.; Comi, Giacomo Pietro; Adnet, P.; Wolz, Werner; Lunardi, Joël; Müller, C. R.; McCarthy, Tommie V.

doi:10.1002/(sici)1098-1004(1998)11:1<45::aid-humu7>3.0.co;2-k

Cited by 41 publications

(17 citation statements)

References 23 publications

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“…In the population analysis, the C7360G nucleotide substitution was not identified in any of the control horses using either Bam HI or SSP. The point mutation found in the MH RyR1 horses is at the same codon reported in two of five mutations for exon 46 in humans 2, 3, 22, 35. In MHS humans, the mutation results in arginine replacement by cysteine or histidine in different families,3, 22 whereas, in our MH RyR1 horses, arginine was replaced by a glycine.…”

Section: Discussionsupporting

confidence: 64%

Furosemide doesn't prevent acute renal failure

2007

Dialysis & Transplantation

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Editor's note:In the interest of continuing to provide you with relevant information you can use directly at the point of patient care, we are introducing Patient‐Oriented Evidence that Matters, or POEMs. InfoPOEMs, owned by John Wiley & Sons, which also publishes D&T, are designed to keep you informed through medical literature and evidence‐based medicine you can apply to your practice. Staff physicians at InfoPOEMs review more than 100 medical journals monthly, and select the best information you can use. They then summarize the study, creating a POEM. These are designed to be synopses, not complete abstracts—they present only the most important information. Each review is supported by a Level of Evidence (LOE) indicator, so you can discern how well this information is supported.POEMs have to meet three criteria: They address a question that you face as clinicians. They measure outcomes that you and your patients care about: symptoms, morbidity, quality of life, and mortality. They have the potential to change the way you practice. We have started with a collection of topics relevant to several aspects of renal care. We will continue to include at least one POEM in each issue. We look forward to your feedback on this newest addition to D&T, and whether we should increase this content.

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Section: Discussionsupporting

confidence: 64%

Furosemide doesn't prevent acute renal failure

2007

Dialysis & Transplantation

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“…The C1843T mutation (R615C) in pigs is located at the N‐terminal region, 4 and is analogous to the C1840T (R614C) and C1841T (R614L) mutations in humans 3 . The mutation in the horse is located in the central region of the gene and is analogous to 2 mutations in MHS in humans: the C7360T (R2454C) and the C7361A (R2454H) mutations 21,22 . Among the known missense mutations in humans, almost half involve an arginine substitution 7 .…”

mentioning

confidence: 99%

“…3 The mutation in the horse is located in the central region of the gene and is analogous to 2 mutations in MHS in humans: the C7360T (R2454C) and the C7361A (R2454H) mutations. 21,22 Among the known missense mutations in humans, almost half involve an arginine substitution. 7 These residue substitutions in humans and horses occur between 2 different groups of amino acids with different physicochemical properties (arginine is a polar strongly basic amino acid whereas glycine is a nonpolar neutral amino acid) resulting in alterations of protein structure and function.…”

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confidence: 99%

Malignant Hyperthermia Associated with Ryanodine Receptor 1 (C7360G) Mutation in Quarter Horses

Aleman¹,

Nieto²,

Magdesian³

2009

Veterinary Internal Medicne

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Background: Anesthetic-induced malignant hyperthermia (MH) has been documented in Quarter Horses with a single point mutation in the ryanodine receptor 1 gene (RyR1) at nucleotide C7360G, generating a R2454G amino acid substitution. However, there have been no reports of nonanesthetic manifestations of MH in horses with the C7360G mutation.Objective: To describe clinical manifestations of Quarter Horses with the C7360G mutation. Animals: Eleven Quarter Horses with the RyR1 C7360G mutation.Methods: This prospective study included horses with suspected MH, undetermined etiology of sudden death, death within hours of onset of rhabdomyolysis, muscle rigidity, stiffness, intermittent sweating, and persistent increases in serum muscle enzyme activities. Whole blood in EDTA and skeletal muscle were processed for genetic and histochemical analysis. Medical records and pedigrees were collected when available.Results: Both anesthetic-and non-anesthetic-associated myopathic manifestations of MH occurred in halter Quarter Horses with mutation of RyR1. The disease is inherited as an autosomal dominant trait. Clinical and laboratory abnormalities were similar in both forms. Rhabdomyolysis was a common finding in both groups of horses. Skeletal muscle histochemical findings were nonspecific and compatible with a noninflammatory myopathic process.Conclusions and Clinical Importance: MH is a potentially fatal disease of Quarter Horses that could be triggered by halogenated anesthetics and other nonanesthetic factors that may include exercise, stress, breeding, illnesses, and concurrent myopathies.

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“…For a limited exclusion of the presence of other causal MH mutations, the PCR products of the following RYR1 exons were purified and directly sequenced using the ABI Prism DNA sequencing kit (big dye terminators, PE Applied Biosystems, Warrington, UK): exons 6, 9, 11, 17, 39, 45, 46. The primers and annealing temperatures were used as described previously [17,20–25].…”

Section: Methodsmentioning

confidence: 99%

Determination of a positive malignant hyperthermia (MH) disposition without the in vitro contracture test in families carrying the RYR1 Arg614Cys mutation

Rueffert¹,

Olthoff²,

Deutrich³

et al. 2001

Clinical Genetics

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Molecular genetic methods are used with caution for determining positive malignant hyperthermia (MH) disposition in clinical MH diagnosis because of the genetic variability of this disease. But under defined conditions, genotyping can have an advantage over the standardized in vitro contracture test (IVCT) in respect of invasive approach, specificity, patient compliance, and the work and expense involved in the method. We aim to demonstrate this using 10 families with the Arg614Cys mutation in the ryanodine receptor as an example. Fifty-one index patients who had been classified as MH-susceptible (MHS) in the IVCT (European MH protocol) after a clinical MH incident or suspected MH were screened for the Arg614Cys (C1840-->T) mutation in the RYR1 gene because this mutation is more common in German MH families (9%). The family members of those index patients, in whom a Arg614Cys mutation was detectable, were also screened for the presence of this mutation (n=136), and the results were subjected to a more detailed analysis including existing IVCT findings (n=71). The Arg614Cys mutation was identified in a total of 64 members of the 10 independent families. In 35 individuals in this group, there was a definite concordance between the MHS diagnosis in the IVCT and the presence of the Arg614Cys mutation. No individual phenotyped as MH-negative carried the mutation. On the basis of the guidelines of the EMHG for molecular genetic detection of MH susceptibility, 29 individuals who bore the Arg614Cys mutation were classified as MHS without the IVCT. If a causal mutation is detected in an MH family, the MHS diagnosis can be deduced without the invasive IVCT in all other mutation carriers. Despite inclusion of only one (Arg614Cys) of all known MH mutations, the study emphasizes the practical use of a genetic approach for determination of a positive MH diagnosis.

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Novel mutations at a CpG dinucleotide in the ryanodine receptor in malignant hyperthermia

Cited by 41 publications

References 23 publications

Furosemide doesn't prevent acute renal failure

Furosemide doesn't prevent acute renal failure

Malignant Hyperthermia Associated with Ryanodine Receptor 1 (C7360G) Mutation in Quarter Horses

Determination of a positive malignant hyperthermia (MH) disposition without the in vitro contracture test in families carrying the RYR1 Arg614Cys mutation

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