|
rs1057518885
|
|
A |
0.700 |
GeneticVariation |
CLINVAR |
|
|
|
|
rs118192123
|
|
|
0.010 |
GeneticVariation |
BEFREE |
The reduction of EC(50) indicates a facilitated calcium release from sarcoplasmic reticulum in the myotubes of the index patient suggesting that the RYR1 Ile2453Thr mutation is pathogenic for the malignant hyperthermia susceptibility and CCD of the two affected individuals.
|
12810058 |
2003 |
|
rs118192124
|
|
|
0.020 |
GeneticVariation |
BEFREE |
Genetic analysis revealed a novel RYR1 mutation that substitutes arginine 2452 for tryptophan in a region of the calcium channel mutated in several other MH pedigrees.
|
10823104 |
2000 |
|
rs118192124
|
|
|
0.020 |
GeneticVariation |
BEFREE |
These results indicate that the R2452W variant results in a hypersensitive ryanodine receptor 1 and suggest that the R2452W variant in the ryanodine receptor 1 is likely to be causative of MH.
|
25086907 |
2014 |
|
rs118192161
|
|
|
0.060 |
GeneticVariation |
BEFREE |
We also present evidence demonstrating that overexpression of wild-type RYR1 in cells obtained from MH-susceptible individuals does not restore the MH-negative phenotype, as far as Ca2+ transients elicited by halothane are concerned; on the other hand, overexpression of a mutated RYR1 Arg163Cys Ca2+ channel in muscle cells obtained from MH-negative individuals conveys hypersensitivity to halothane.
|
9502764 |
1998 |
|
rs118192161
|
|
|
0.060 |
GeneticVariation |
BEFREE |
RYR1 mutations associated with both CCD and MH (R163C, R2163H, R2435H) had more severe caffeine and halothane response phenotypes than those associated with MH alone.
|
12124989 |
2002 |
|
rs118192161
|
|
|
0.060 |
GeneticVariation |
BEFREE |
Heterozygous R163C mice represent a valid model for studying the mechanisms that cause the human malignant hyperthermia syndrome.
|
17122579 |
2006 |
|
rs118192161
|
|
|
0.060 |
GeneticVariation |
BEFREE |
We report here that one of these, the Arg163Cys substitution, does not cosegregate with MH susceptibility.
|
8592342 |
1995 |
|
rs118192161
|
|
|
0.060 |
GeneticVariation |
BEFREE |
The frequencies of occurrence of the C1840T and C487T mutations were 2% and 1%, respectively, in MH-positive subjects and were the only two mutations identified.
|
7547049 |
1995 |
|
rs118192161
|
|
|
0.060 |
GeneticVariation |
BEFREE |
Considering that many MH symptoms resemble those that could ensue from a mitochondrial dysfunction (e.g. metabolic acidosis and hyperthermia) and that MH-susceptible mice or humans have a higher than normal cytoplasmic Ca(2+) concentration at rest, we evaluated the role of mitochondria in skeletal muscle from R163C compared with wild type mice under basal (untriggered) conditions.
|
20978128 |
2011 |
|
rs118192162
|
|
|
0.060 |
GeneticVariation |
BEFREE |
Knock-in mice with the malignant hyperthermia susceptibility RYR1 mutation Y522S (MHS RYR1Y522S) had longer bleeding times than their wild-type littermates.
|
27382027 |
2016 |
|
rs118192162
|
|
|
0.060 |
GeneticVariation |
BEFREE |
Mice (Y522S or YS), carrying a mutation of the sarcoplasmic reticulum (SR) Ca<sup>2+</sup> release channel of skeletal muscle fibers (ryanodine receptor type-1, RyR1) which causes Ca<sup>2+</sup> leak, are a widely accepted and intensively studied model for human malignant hyperthermia (MH) susceptibility.
|
31607937 |
2019 |
|
rs118192162
|
|
|
0.060 |
GeneticVariation |
BEFREE |
Denaturing high performance liquid chromatography screening of ryanodine receptor type 1 gene in patients with malignant hyperthermia in Taiwan and identification of a novel mutation (Y522C).
|
16244001 |
2005 |
|
rs118192162
|
|
|
0.060 |
GeneticVariation |
BEFREE |
Cytosolic and mitochondrial Ca(2+) transients induced by caffeine stimulation were drastically augmented in the MH mutant, slightly reduced in one CCD mutant (Y523S) and completely abolished in another (I4898T).
|
15689621 |
2005 |
|
rs118192162
|
|
|
0.060 |
GeneticVariation |
BEFREE |
Mice with a malignant hyperthermia mutation (Y522S) in the ryanodine receptor (RyR1) display muscle contractures, rhabdomyolysis, and death in response to elevated environmental temperatures.
|
18394989 |
2008 |
|
rs118192162
|
|
|
0.060 |
GeneticVariation |
BEFREE |
We confirmed the in vivo significance by using mice with a knock-in mutation (Y524S) in the type I ryanodine receptor (Ryr1), a mutation analogous to the Y522S mutation associated with MH in humans.
|
29930394 |
2019 |
|
rs118192163
|
|
|
0.030 |
GeneticVariation |
BEFREE |
RYR1 mutations associated with both CCD and MH (R163C, R2163H, R2435H) had more severe caffeine and halothane response phenotypes than those associated with MH alone.
|
12124989 |
2002 |
|
rs118192163
|
|
|
0.030 |
GeneticVariation |
BEFREE |
Here we report the identification by two independent methods of a novel mutation associated with the MH-susceptible phenotype in the RYR1 gene: the 6488G-->C transversion, resulting in the replacement of the Arg2163 with a proline residue.
|
10757649 |
2000 |
|
rs118192163
|
|
|
0.030 |
GeneticVariation |
BEFREE |
However, maximal VGCR was reduced only for MH + CCD mutants (Y4795C, R2435L, and R2163H) in which spontaneous Ca2+ oscillations occurred with significantly longer duration (Y4795C and R2435L) or higher frequency (R2163H).
|
15347586 |
2004 |
|
rs118192167
|
|
|
0.010 |
GeneticVariation |
BEFREE |
However, maximal VGCR was reduced only for MH + CCD mutants (Y4795C, R2435L, and R2163H) in which spontaneous Ca2+ oscillations occurred with significantly longer duration (Y4795C and R2435L) or higher frequency (R2163H).
|
15347586 |
2004 |
|
rs118192168
|
|
|
0.010 |
GeneticVariation |
BEFREE |
Phenotype-genotype correlation analysis indicates that the presence of the triplet allele alone confers susceptibility to MH, and that the presence of this allele in a compound heterozygous state with the MH-associated RYR1 variant c.14545G>A (p.Val4849Ile) results in the MH susceptibility phenotype and a congenital myopathy with cores and rods.
|
25958340 |
2015 |
|
rs118192170
|
|
|
0.010 |
GeneticVariation |
BEFREE |
Cytosolic and mitochondrial Ca(2+) transients induced by caffeine stimulation were drastically augmented in the MH mutant, slightly reduced in one CCD mutant (Y523S) and completely abolished in another (I4898T).
|
15689621 |
2005 |
|
rs118192172
|
|
|
0.090 |
GeneticVariation |
BEFREE |
Genetic screening for MH-related mutations in the RYR1 gene revealed the presence of a homozygous 1840C-->T base exchange (Arg614Cys substitution) in this patient.
|
11493496 |
2001 |
|
rs118192172
|
|
|
0.090 |
GeneticVariation |
BEFREE |
Screening for these 21 mutations in 105 MH families including 10 CCD families phenotyped by the in vitro contracture test (IVCT) according to the European protocol revealed the following approximate distribution: 9% Arg-614-Cys, 1% Arg-614-Leu, 1% Arg-2163-Cys, 1% Val-2168-Met, 3% Thr-2206-Met and 7% Gly-2434-Arg.
|
10484775 |
1999 |
|
rs118192172
|
|
|
0.090 |
GeneticVariation |
BEFREE |
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.
|
11553045 |
2001 |