2018
DOI: 10.1085/jgp.201812160
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The homozygous K280N troponin T mutation alters cross-bridge kinetics and energetics in human HCM

Abstract: Hypertrophic cardiomyopathy (HCM) is a genetic form of left ventricular hypertrophy, primarily caused by mutations in sarcomere proteins. The cardiac remodeling that occurs as the disease develops can mask the pathogenic impact of the mutation. Here, to discriminate between mutation-induced and disease-related changes in myofilament function, we investigate the pathogenic mechanisms underlying HCM in a patient carrying a homozygous mutation (K280N) in the cardiac troponin T gene (TNNT2), which results in 100% … Show more

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Cited by 26 publications
(21 citation statements)
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“…We have also studied a heart muscle sample from a patient with an HCM-causing mutation [homozygous TNNT2 K280N (Sequeira et al, 2013;Messer et al, 2016;Piroddi et al, 2019)]. The patient had a myectomy operation that relieved LVOTO permanently but later developed heart failure requiring a heart transplant.…”
Section: Normal Level Of Phosphorylation In Hcm Samples Without Pressmentioning
confidence: 99%
“…We have also studied a heart muscle sample from a patient with an HCM-causing mutation [homozygous TNNT2 K280N (Sequeira et al, 2013;Messer et al, 2016;Piroddi et al, 2019)]. The patient had a myectomy operation that relieved LVOTO permanently but later developed heart failure requiring a heart transplant.…”
Section: Normal Level Of Phosphorylation In Hcm Samples Without Pressmentioning
confidence: 99%
“…Unpublished data Table 1 Kinetic parameters of mouse and human ventricular myofibrils following replacement by exchange of the endogenous cTn complex with human recombinant cTn Data are mean ± SEM; n ≥ 10. Data from human cTn exchanged mouse myofibrils and control (sham-treated) mouse myofibrils are unpublished data; data from human cTn exchanged human ventricular myofibrils are from Piroddi et al (2019). The exchange protocol allows replacement of 70-90% of the endogenous cTn complex Myofibril type To better interpret myofibril tension kinetic parameters in terms of apparent CB kinetics we need a description of the reaction pathway for acto-myosin ATPase and energy-transduction cycle.…”
Section: Myofibrils and Fast Solution Switching: Experimental Tools Tmentioning
confidence: 99%
“…Remarkably, higher energy cost in HCM muscle strips appears to be a feature shared by different mutations. This was recently corroborated in homozygous K280N-troponin T samples, which showed 24-72% higher values than three different control groups, that was ascribed to faster cross-bridge detachment [34].…”
Section: Trends Trends In In Molecular Molecular Medicine Medicinementioning
confidence: 57%