]> 2026-07-31T11:51:59+00:00 WBR0120 0 en Beta-myosin Potassium ion channel Long QT syndromes, such as LQT1 and LQT2, are caused by potassium channel gene mutations ''KCNQ1'' and ''KCNE2'', respectively. Also, Jervell and Lange-Nielsen (JLN) syndrome is a rare but clinically significant long QT syndrome that involves potassium channel mutations. Calcium ion channel Among patients with intolerance to beta-blocker, patients with HOCM can be treated with a calcium channel blocker, such as verapamil, to decrease myocardial contractility. Calcium ion channel mutations are associated with neurological diseases. Ryanodine receptor Mutation of the ryanodine receptor is associated with malignant hyperthermia (MH). The ryanodine receptor ''RYR1'' gene encodes calcium release in skeletal muscles. Patients with a mutated ''RYR1'' are susceptible to MH. Myostatin Hypertrophic Obstructive Cardiomyopathy (HOCM) is an autosomal dominant genetic disorder. It is caused by a missense mutation in 1 of at least 14 genes that encode cardiac sarcomeres. Most common mutations encode beta-myosin heavy chain (MYH7) and cardiac myosin binding protein C (MYBPC3). HOCM is characterized by a hypertrophic cardiomyopathy that involves the ventricular septum, resulting in dynamic left ventricular outflow tract obstruction, mitral regurgitation, and diastolic dysfunction. The majority of patients lead a normal life. Some experience symptoms of myocardial ischemia such as angina and dyspnea; and a minority of patients suffer ventricular arrhythmias and die at young age. HOCM may be diagnosed incidentally during routine physical examination or work-up. The most important finding suggestive of HOCM on physical examination is a systolic ejection murmur best heard at the left sternal bordern (LSB) that increases in intensity during maneuvers the decrease preload, such as standing from a squatting position. ECG findings include evidence of left ventricular hypertrophy. The definitive diagnosis of HOCM is made by 2-D echocardiography, which demonstrates asymmetric hypertrophy of the myocardium with a septal thickness greater than the thickness of the free well, and continuous-wave Doppler echocardiography, which reveals resting obstruction. Myocardial biopsy is not required, but it demonstrates myofibrillar disarray, myocyte hypertrophy, and fibrosis. Management of patients with HOCM includes symptomatic relief using beta-blockers of verapamil. Other prophylactic measures include infective endocarditis prophylaxis, avoidance of high intensity exercise or dehydration, genetic counseling, and period screening for other immediate family members. Surgical intervention by septal myomectomy is rarely required.<br/> '''Educational Objective:''' Hypertrophic Obstructive Cardiomyopathy (HOCM) is an autosomal dominant genetic disorder. It is caused by a missense mutation in 1 of at least 14 genes that encode cardiac sarcomeres. Most common mutations encode beta-myosin heavy chain (MYH7) and cardiac myosin binding protein C (MYBPC3).<br/> '''References:''' McCarthy TV, Quane KA, Lynch PJ. Ryanodine receptor mutations in malignant hyperthermia and central core disease. Hum Mutat. 2000;15(5):410-7 Mosher DS, Quignon P, Bustamante CD, et al. A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygous dogs. PLoS Genet. 2007;3(5):e79 Nader A, Massumi A, Cheng J, et al. Inherited arrhythmic disorders: long QT and Brugada syndromes. Tex Heart Inst J. 2007;34(1):67-75 Nishimura RA, Holmes DR. Hypertrophic obstructive cardiomyopathy. N Engl J Med. 2004;350:1320-7 Roncarati R, Latronico MV, Musumeci B, et al. Unexpectedly low mutation rates in beta-myosin heavy chain and cardiac myosin binding protein genes in Italian patients with hypertrophic cardiomyopathy. J Cell Physiol. 2011;226(11):2894-900. First Aid 2014 page 290 Genetics An 22-year-old man collapses while playing during a basketball game. Despite appropriate cardiopulmonary resuscitation efforts, the patient is finally pronounced dead. At autopsy, toxicological tests are negative for alcohol or illicit drugs. The pathologist further notes a large, thick myocardium with disarrayed muscle fibers. He concludes that the patient died of an arrhythmia. Mutation in the gene encoding which of the following proteins most likely caused the patient's condition? A Cardiology 2020-10-27T23:24:40Z 2459150.475463 WBR0120