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Ryanodine receptor mutations in malignant hyperthermia and central core disease

Overview of attention for article published in Human Mutation, May 2000
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2 tweeters

Citations

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331 Dimensions

Readers on

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75 Mendeley
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Title
Ryanodine receptor mutations in malignant hyperthermia and central core disease
Published in
Human Mutation, May 2000
DOI 10.1002/(sici)1098-1004(200005)15:5<410::aid-humu2>3.0.co;2-d
Pubmed ID
Authors

Tommie V. McCarthy, Kathleen A. Quane, Patrick J. Lynch

Abstract

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that manifests in response to anesthetic triggering agents. Central core disease (CCD) is a myopathy closely associated with MH. Both MH and CCD are primarily disorders of calcium regulation in skeletal muscle. The ryanodine receptor (RYR1) gene encodes the key channel which mediates calcium release in skeletal muscle during excitation-contraction coupling, and mutations in this gene are considered to account for susceptibility to MH (MHS) in more than 50% of cases and in the majority of CCD cases. To date, 22 missense mutations in the 15,117 bp coding region of the RYR1 cDNA have been found to segregate with the MHS trait, while a much smaller number of these mutations is associated with CCD. The majority of RYR1 mutations appear to be clustered in the N-terminal amino acid residues 35-614 (MH/CCD region 1) and the centrally located residues 2163-2458 (MH/CCD region 2). The only mutation identified outside of these regions to date is a single mutation associated with a severe form of CCD in the highly conserved C-terminus of the gene. All of the RYR1 mutations result in amino acid substitutions in the myoplasmic portion of the protein, with the exception of the mutation in the C-terminus, which resides in the lumenal/transmembrane region. Functional analysis shows that MHS and CCD mutations produce RYR1 abnormalities that alter the channel kinetics for calcium inactivation and make the channel hyper- and hyposensitive to activating and inactivating ligands, respectively. The likely deciding factors in determining whether a particular RYR1 mutation results in MHS alone or MHS and CCD are: sensitivity of the RYR1 mutant proteins to agonists; the level of abnormal channel-gating caused by the mutation; the consequential decrease in the size of the releasable calcium store and increase in resting concentration of calcium; and the level of compensation achieved by the muscle with respect to maintaining calcium homeostasis. From a diagnostic point of view, the ultimate goal of development of a simple non-invasive test for routine diagnosis of MHS remains elusive. Attainment of this goal will require further detailed molecular genetic investigations aimed at solving heterogeneity and discordance issues in MHS; new initiatives aimed at identifying modulating factors that influence the penetrance of clinical MH in MHS individuals; and detailed studies aimed at describing the full epidemiological picture of in vitro responses of muscle to agents used in diagnosis of MH susceptibility.

Twitter Demographics

The data shown below were collected from the profiles of 2 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 75 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Switzerland 1 1%
Ireland 1 1%
Brazil 1 1%
Slovenia 1 1%
Japan 1 1%
Unknown 70 93%

Demographic breakdown

Readers by professional status Count As %
Student > Master 16 21%
Student > Bachelor 15 20%
Student > Ph. D. Student 11 15%
Researcher 6 8%
Other 5 7%
Other 14 19%
Unknown 8 11%
Readers by discipline Count As %
Agricultural and Biological Sciences 21 28%
Medicine and Dentistry 20 27%
Biochemistry, Genetics and Molecular Biology 14 19%
Nursing and Health Professions 2 3%
Chemistry 2 3%
Other 5 7%
Unknown 11 15%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 January 2022.
All research outputs
#13,595,706
of 20,983,497 outputs
Outputs from Human Mutation
#2,114
of 2,806 outputs
Outputs of similar age
#133,635
of 248,097 outputs
Outputs of similar age from Human Mutation
#14
of 24 outputs
Altmetric has tracked 20,983,497 research outputs across all sources so far. This one is in the 33rd percentile – i.e., 33% of other outputs scored the same or lower than it.
So far Altmetric has tracked 2,806 research outputs from this source. They receive a mean Attention Score of 4.4. This one is in the 22nd percentile – i.e., 22% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 248,097 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 24 others from the same source and published within six weeks on either side of this one. This one is in the 41st percentile – i.e., 41% of its contemporaries scored the same or lower than it.