|
rs118192177
|
|
|
0.720 |
GeneticVariation |
BEFREE |
In this study we could demonstrate that the MH causative Thr2206Met mutation may also be associated both with clinical symptoms of a mild myopathy and histopathological changes in the oxidative inter myofibrillar network.
|
19919814 |
2010 |
|
rs118192177
|
|
|
0.720 |
GeneticVariation |
BEFREE |
From the reduction of EC(50) we conclude that the RyR1 Thr2206Met mutation is pathogenic for MH.
|
12220451 |
2002 |
|
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 |
|
rs118192172
|
|
|
0.090 |
GeneticVariation |
BEFREE |
A cysteine-for-arginine substitution (R614C) in the human skeletal muscle calcium release channel cosegregates with malignant hyperthermia.
|
1510267 |
1992 |
|
rs118192172
|
|
|
0.090 |
GeneticVariation |
BEFREE |
A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia.
|
1774074 |
1991 |
|
rs118192172
|
|
|
0.090 |
GeneticVariation |
BEFREE |
Because there is strong evidence supporting the causal nature of the Arg614Cys mutation, the discordant persons are not closely related within the pedigree as they would be if a second MH mutation were segregating, and the CHCT is not 100% accurate, we propose that the observed discordance between DNA test results and CHCT assignment in this kindred results from two false-positive diagnoses by the CHCT.
|
8602662 |
1996 |
|
rs118192172
|
|
|
0.090 |
GeneticVariation |
BEFREE |
Several observations support the view that a single RYR1 mutation is causal of malignant hyperthermia in all breeds of pigs and in at least some human families: the substitution of Cys for Arg615 as the sole deduced amino acid sequence change in a comparison of malignant hyperthermia and normal porcine RYR1 cDNAs; the linkage of this mutation to malignant hyperthermia in over 450 pigs in six breeds, including 338 meioses; and the appearance of the corresponding mutation, Cys for Arg614, across a species barrier, in a few human families, where it also cosegregates with malignant hyperthermia.
|
1329295 |
1992 |
|
rs118192172
|
|
|
0.090 |
GeneticVariation |
BEFREE |
These findings may suggest that it is necessary to reconsider the specificity of the IVCT and the role of C1840T as a cause of MH susceptibility in some families exhibiting this mutation.
|
9520251 |
1997 |
|
rs118192172
|
|
|
0.090 |
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 |
|
rs121918593
|
|
|
0.070 |
GeneticVariation |
BEFREE |
The substitution of Arg for Gly2433 in the human skeletal muscle ryanodine receptor is associated with malignant hyperthermia.
|
7881417 |
1994 |
|
rs121918593
|
|
|
0.070 |
GeneticVariation |
BEFREE |
One MH mutation (Gly2434Arg) was found in one MHS individual.
|
15281512 |
2004 |
|
rs121918593
|
|
|
0.070 |
GeneticVariation |
BEFREE |
In the first extensive UK population survey, eight of 15 mutations were detected in 85 out of 297 (29%) unrelated MH susceptible cases, with G2434R detected in 53 cases (18%).
|
12124989 |
2002 |
|
rs121918593
|
|
|
0.070 |
GeneticVariation |
BEFREE |
The human p.G2434R variant of the RYR1 gene is most frequently associated with malignant hyperthermia (MH) in the UK.
|
30236258 |
2018 |
|
rs121918593
|
|
|
0.070 |
GeneticVariation |
BEFREE |
Malignant hyperthermia causing Gly2435Arg mutation of the ryanodine receptor facilitates ryanodine-induced calcium release in myotubes.
|
10700782 |
1999 |
|
rs121918593
|
|
|
0.070 |
GeneticVariation |
BEFREE |
Furthermore we identify a high-risk cluster of haplotypes that is associated with the commonest UK MH mutation p.G2434R/c.7300G>A.
|
18945287 |
2009 |
|
rs121918593
|
|
|
0.070 |
GeneticVariation |
BEFREE |
We identified 9 heterozygous RYR1 mutations/variants in 14 families, 5 of them (p.Lys1393Arg; p.Gly2434Arg; p.Thr4288_Ala4290dup; p.Ala4295Val; and p.Arg4737Gln) previously associated with MH.
|
23628358 |
2013 |
|
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 |