Discordance between malignant hyperthermia susceptibility and RYR1 mutation C1840T in two Scandinavian MH families exhibiting this mutation

Fagerlund, T. H.; Ørding, Helle; Bendixen, D.; Islander, Gunilla; Twetman, Eva Ranklev; Berg, Kåre

doi:10.1111/j.1399-0004.1997.tb02561.x

Cited by 30 publications

(5 citation statements)

References 17 publications

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“…MH is genetically heterogeneous and discordance between IVCT phenotype and RYR1 genotype has been reported in both IVCT-positive (MHS) and IVCT-negative (MH normal [MHN]) patients (Adeokun et al, 1997;Deufel et al, 1995;Fagerlund et al, 1997). On retrospective analysis of European MH families with an identified RYR1 mutation, an individual without the familial mutation tested positive by the IVCT in 2.5% of families (n 5 196) investigated [Robinson et al, 2003a].…”

Section: Clinical and Diagnostic Relevancementioning

confidence: 99%

Mutations inRYR1in malignant hyperthermia and central core disease

et al. 2006

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The RYR1 gene encodes the skeletal muscle isoform ryanodine receptor and is fundamental to the process of excitation-contraction coupling and skeletal muscle calcium homeostasis. Mapping to chromosome 19q13.2, the gene comprises 106 exons and encodes a protein of 5,038 amino acids. Mutations in the gene have been found in association with several diseases: the pharmacogenetic disorder, malignant hyperthermia (MH); and three congenital myopathies, including central core disease (CCD), multiminicore disease (MmD), and in an isolated case of a congenital myopathy characterized on histology by cores and rods. The majority of gene mutations reported are missense changes identified in cases of MH and CCD. In vitro analysis has confirmed that alteration of normal calcium homeostasis is a functional consequence of some of these changes. Genotype-phenotype correlation studies performed using data from MH and CCD patients have also suggested that mutations may be associated with a range of disease severity phenotypes. This review aims to summarize the current understanding of RYR1 mutations reported in association with MH and CCD and the present viewpoint on the use of mutation data to aid clinical diagnosis of these conditions.

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Section: Clinical and Diagnostic Relevancementioning

confidence: 99%

Mutations inRYR1in malignant hyperthermia and central core disease

et al. 2006

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“…Families from Sweden were reported to exhibit the Arg614Cys mutation; however, it was found infrequently (1 5, 16). The Argl63Cys, Gly341Arg, Ile403Met and Arg2434His mutations were not found to occur in a Scandavian population (17). The lack, or weak association, of these RYRI mutations in the North American pedigrees examined suggests that other mutations in the RYRl or mutations in additional genes predominate in producing the MH syndrome in North America.…”

Section: Resultsmentioning

confidence: 95%

Failure to identify the ryanodine receptor G1021A mutation in a large North American population with malignant hyperthermia

1998

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Anesthesia‐induced malignant hyperthermia (MH) is a rare inherited disorder of skeletal muscle. Several mutations in the ryanodine receptor (RYR1) have been found to be causative of MH. The G1021A mutation in the RYR1 is one of the most frequently occurring mutations in European populations. MH normal (165) and MH susceptible (114) North American patients were screened for the presence of the G1021A mutation. This mutation was not found in any of the patients tested. These studies support the absence of this mutation in the normal population. Furthermore, these findings emphasize the importance of viewing the distribution of MH mutations as variable gene pools with frequencies dependent on the geographical location of the population examined.

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“…Although mutations in the ryanodine receptor appear to be an important factor in the [1,48] The presence of a mutation also does not explain the interindividual and intraindividual variability in the clinical expression of MH syndrome. In several families, there has been discordance between the MH ryanodine genotype and phenotype as determined by the in vitro caffeine halothane contracture test (IVCT) [49][50][51][52][53].…”

Section: Pathophysiologymentioning

confidence: 99%