Hypertrophic cardiomypathy

A single missense variant of the TMPO /LAP2α gene, encoding LAP2 proteins, has been associated with cardiomyopathy in two brothers. To further evaluate its role in cardiac muscle, we included TMPO in our cardiomyopathy diagnostic gene panel. A screening of ~5000 patients revealed three novel rare TMPO heterozygous variants in six males diagnosed with hypertrophic or dilated cardiomypathy. We identified in different cellular models that (1) the frameshift variant LAP2α p.(Gly395Glufs*11) induced haploinsufficiency, impeding cell proliferation and/or producing a truncated protein mislocalized in the cytoplasm; (2) the C-ter missense variant LAP2α p...

HCM is the most common inherited heart condition occurring in 1:500 individuals in the general population. Left ventricular outflow obstruction at rest or after provocation occurs in 2/3 of HCM patients and is a frequent cause of limiting symptoms. Pharmacologic therapy is the first-line treatment for obstruction, and should be aggressively pursued before application of invasive therapy. Beta-blockade is given first, and up-titrated to decrease resting heart rate to between 50 and 60 beats per minute. However, beta-blockade is not expected to decrease resting gradients; its effect rests on decreasing the rise in gradient that accompanies exercise...

Cardioplegic arrest and cardiopulmonary bypass are key triggers of myocardial injury during aortic valve surgery. Cardioplegic ischaemic arrest is associated with disruption to metabolic and ionic homeostasis in cardiomyocytes. These changes predispose the heart to reperfusion injury caused by elevated intracellular reactive oxygen species and calcium. Cardiopulmonary bypass is associated with an inflammatory response that can generate systemic oxidative stress which, in turn, provokes further damage to the heart...

Cardiomyopathies are myocardial diseases in which there is structural and functional disorder of the heart muscle, in the absence of coronary artery disease, hypertension, valvular disease and congenital heart disease. Cardiomyopathies are grouped into specific morphological and functional phenotypes: dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and unclassified cardiomyopathies. Patients with dilated and hypertrophic cardiomypathy are prone to the development of congestive heart failure in the perioperative period...

Diagnosis of primarly cardiomypathies refers to genes discorders in chromosomes. Aim of this paper is to show genetics and molecular knowledges published so far. Familiar form hypertrophic cardiomyopathy is hereditable autosomatically dominantly in any of 10 genes that regulate contractile, structural and regulative function with predomination of mutation in gene for heavy chaire of myocardiac beta myosin localized at 14 chromosome (more than 200 mutation). Sporadic forms appears autosomatically recessively as the result of new mutation or as non-genetic form...

BACKGROUND: Electrocardiograms in elite endurance athletes sometimes show bizarre patterns suggestive of inherited channelopathies (Brugada syndrome, long QTc, catecholaminergic polymorphic ventricular tachycardia) and cardiomyopathies (arrhythmogenic right ventricular cardiomyopathy, hypertrophic cardiomyopathy) responsible for unexpected sudden cardiac death. Among other methods, genetic analyses are required for correct diagnosis. OBJECTIVE: To correlate 12-lead electrocardiographic patterns suggestive of inherited channelopathies and cardiomyopathies to specific genetic analyses...

Cardiac myosin binding protein C (cMyBP-C), bound to the sarcomere's myosin thick filament, plays an important role in the regulation of muscle contraction. cMyBP-C is a large multidomain protein that interacts with myosin, titin, and possibly actin. Mutations in cMyBP-C are the most common known cause of heritable hypertrophic cardiomypathies. Phosphorylation of cMyBP-C plays an essential role in the normal cardiac function. cMyBP-C (142 kDa) has 81 serine and 73 threonine residues presenting a major challenge for unequivocal identification of specific phosphorylation sites...

Fabry's disease is a rare lysosomal storage disease caused by the X-linked defect of the enzyme alpha-galactosidase A leading to the intracellular accumulation of glycosphingolipids in various organs and tissues. Cardiac involvement is frequent and, in individuals with some residual enzyme activity, may be the sole manifestation of the disease. Hemizygous men are generally more seriously affected than heterozygous women. The dominant cardiac manifestations include myocardial hypertrophy of the left ventricle, which, in some patients, mimics hypertrophic cardiomypathy...