|
Hypertrophic Cardiomyopathy
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Strong cross-bridges potentiate the Ca(2+) affinity changes produced by hypertrophic cardiomyopathy cardiac troponin C mutants in myofilaments: a fast kinetic approach.
|
21056975 |
2011 |
|
Hypertrophic Cardiomyopathy
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Mutations in TNNC1-encoded cardiac troponin C (cTnC) are a relatively rare cause of HCM.
|
22815480 |
2012 |
|
Hypertrophic Cardiomyopathy
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
We used a murine model of hypertrophic cardiomyopathy (HCM) harboring a cardiac troponin C (cTnC) Ca<sup>2+</sup>-sensitizing mutation, Ala8Val in the regulatory N-domain.
|
30138628 |
2018 |
|
Hypertrophic Cardiomyopathy
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Because all the known disease genes encode major contractile elements in cardiac muscle, we have systematically characterized the cardiac sarcomere genes, including cardiac troponin I (cTnI), cardiac actin (cACT) and cardiac troponin C (cTnC) in 184 unrelated patients with HCM and found mutations in the cTnI gene in several patients.
|
9241277 |
1997 |
|
Hypertrophic Cardiomyopathy
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Two novel mutations (G159D and L29Q) in cardiac troponin C (CTnC) associate their phenotypic outcomes with dilated (DCM) and hypertrophic cardiomyopathy (HCM), respectively.
|
18820258 |
2008 |
|
Hypertrophic Cardiomyopathy
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Cardiac troponin C-L29Q, related to hypertrophic cardiomyopathy, hinders the transduction of the protein kinase A dependent phosphorylation signal from cardiac troponin I to C.
|
16302972 |
2005 |
|
Hypertrophic Cardiomyopathy
|
0.500 |
Biomarker
|
disease |
BEFREE |
The goal of this study was to determine whether TNNC1 can be categorized as an hypertrophic cardiomyopathy susceptibility gene, such that a mouse model can recapitulate the clinical presentation of the proband.
|
26304555 |
2015 |
|
Hypertrophic Cardiomyopathy
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Therefore, we reconstituted rabbit soleus fibers and bovine masseter myofibrils with mutant cTnCs (A8V, C84Y, E134D, and D145E) associated with HCM to investigate their effects on contractile force and ATPase rates, respectively.
|
28473771 |
2017 |
|
Hypertrophic Cardiomyopathy
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Characterization of the L29Q Hypertrophic Cardiomyopathy Mutation in Cardiac Troponin C by Paramagnetic Relaxation Enhancement Nuclear Magnetic Resonance.
|
30620548 |
2019 |
|
Hypertrophic Cardiomyopathy
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
To assess whether this functional phenomenon was a direct result of altered Ca(2+) affinity or was caused by altered troponin-tropomyosin switching, we assessed Ca(2+) binding of the regulatory site of cardiac troponin C in wild-type or mutant troponin complex and thin filaments using a fluorescent probe (2-[4'-{iodoacetamido}aniline]-naphthalene-6-sulfonate) attached to Cys35 of cardiac troponin C. The Ca(2+)-binding affinity (pCa(50)=6.57+/-0.03) of reconstituted troponin complex was unaffected by all of the HCM and dilated cardiomyopathy troponin mutants tested, with the exception of the troponin I Arg145Gly HCM mutation, which caused an increase (DeltapCa(50)=+0.31+/-0.05).
|
17932326 |
2007 |
|
Hypertrophic Cardiomyopathy
|
0.500 |
Biomarker
|
disease |
BEFREE |
Our results (i) confirm that genetic backgrounds of hypertrophic cardiomyopathy and restrictive cardiomyopathy overlap and (ii) indicate that TNNC1 is a likely novel gene for autosomal recessive restrictive cardiomyopathy.
|
27604170 |
2016 |
|
Hypertrophic Cardiomyopathy
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
The cardiac troponin C mutation Leu29Gln found in a patient with hypertrophic cardiomyopathy does not alter contractile parameters in skinned murine myocardium.
|
19506933 |
2009 |
|
Hypertrophic Cardiomyopathy
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Enhanced troponin I binding explains the functional changes produced by the hypertrophic cardiomyopathy mutation A8V of cardiac troponin C.
|
26976709 |
2016 |
|
Hypertrophic Cardiomyopathy
|
0.500 |
Biomarker
|
disease |
BEFREE |
This study may help to further define TNNC1 as an HCM-susceptibility gene, a classification that has already been established for the other members of the troponin complex.
|
18572189 |
2008 |
|
Hypertrophic Cardiomyopathy
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Here, we used high-resolution electron-spray ionization mass spectrometry (ESI-MS), Carr-Purcell-Meiboom-Gill relaxation dispersion (CPMG-RD), and affinity measurements of cTnC for the thin filament in reconstituted papillary muscles to provide evidence of an allosteric mechanism in mutant cTnC that may play a role to the HCM phenotype.
|
28049727 |
2017 |
|
Hypertrophic Cardiomyopathy
|
0.500 |
GeneticVariation
|
disease |
BEFREE |
Effects of calcium binding and the hypertrophic cardiomyopathy A8V mutation on the dynamic equilibrium between closed and open conformations of the regulatory N-domain of isolated cardiac troponin C.
|
23425245 |
2013 |
|
Cardiomyopathies
|
0.350 |
GeneticVariation
|
group |
BEFREE |
These in vivo alterations further implicate the role of TNNC1 mutations in the development of cardiomyopathy.
|
26304555 |
2015 |
|
Cardiomyopathies
|
0.350 |
PosttranslationalModification
|
group |
BEFREE |
Modulation of cardiac troponin C function by the cardiac-specific N-terminus of troponin I: influence of PKA phosphorylation and involvement in cardiomyopathies.
|
18042489 |
2008 |
|
Cardiomyopathies
|
0.350 |
GeneticVariation
|
group |
BEFREE |
Our results provide novel evidence that modification of the cTnC-cTnI interaction has distinct effects on troponin Ca(2+)-binding and cross-bridge kinetics to suggest a novel role for thin filament mutations in the modulation of myofilament function through beta-adrenergic signaling as well as the development of cardiomyopathy.
|
17446435 |
2007 |
|
Cardiomyopathies
|
0.350 |
GeneticVariation
|
group |
BEFREE |
Challenging current paradigms related to cardiomyopathies. Are changes in the Ca2+ sensitivity of myofilaments containing cardiac troponin C mutations (G159D and L29Q) good predictors of the phenotypic outcomes?
|
18820258 |
2008 |
|
Cardiomyopathies
|
0.350 |
Biomarker
|
group |
BEFREE |
Due to its role in contraction, cTnC has been a therapeutic target in the search for small molecules to treat conditions that interfere with normal muscle contraction like the heritable cardiomyopathies.
|
31141358 |
2019 |
|
Cardiomyopathy, Dilated
|
0.180 |
GeneticVariation
|
group |
BEFREE |
Mutations in cardiac troponin C (D75Y, E59D, and G159D), a key regulatory protein of myofilament contraction, have been associated with dilated cardiomyopathy (DCM).
|
27133568 |
2016 |
|
Cardiomyopathy, Dilated
|
0.180 |
GeneticVariation
|
group |
BEFREE |
Recently, mutations in cTnC have been associated with hypertrophic or dilated cardiomyopathy.
|
26232335 |
2015 |
|
Cardiomyopathy, Dilated
|
0.180 |
GeneticVariation
|
group |
BEFREE |
The dilated cardiomyopathy G159D mutation in cardiac troponin C weakens the anchoring interaction with troponin I.
|
18803402 |
2008 |
|
Cardiomyopathy, Dilated
|
0.180 |
GeneticVariation
|
group |
BEFREE |
We recently reported a dilated cardiomyopathy (DCM) causing mutation in a novel disease gene, TNNC1, which encodes cardiac troponin C (TnC).
|
17021793 |
2007 |