Expanded Spectrum of Gene Causing Both Hypertrophic Cardiomyopathy and Dilated Cardiomyopathy

Abstract

See related articles, pages 375–382 Cardiomyopathy can be classified into at least four main forms, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), restrictive cardiomyopathy, and left ventricular noncompaction. HCM produces ventricular wall thickening, especially in the interventricular septum, with decrease in ventricular chamber volumes. DCM produces a prominent increase in chamber volumes without ventricular wall thickening. In HCM, systolic function is increased or at least preserved, whereas diastolic function is impaired in part because of the hypertrophy itself, interstitial fibrosis, and/or myocyte disarrays. Diastolic dysfunction is thought to be responsible for symptoms of heart failure and premature sudden cardiac death of HCM patients. In contrast, DCM is characterized by systolic dysfunction, which leads to congestive heart failure requiring cardiac transplantation. Restrictive cardiomyopathy is characterized by restrictive diastolic dysfunction (restrictive filling and reduced diastolic volume of either or both ventricles) with normal or near normal systolic function and wall thickness. Left ventricular noncompaction is characterized by deep trabeculation in the ventricular wall with systolic and diastolic dysfunction, arrhythmias, and thromboembolic events. More than 400 mutations that cause HCM, DCM, restrictive cardiomyopathy, and left ventricular noncompaction have been found in the genes for proteins constituting the sarcomere of cardiac muscle in human, including α- and β-myosin heavy chains, α-cardiac actin, cardiac troponin (cTn)T, cTnI, cTnC, α-tropomyosin (αTM), cardiac myosin-binding protein-C, cardiac myosin essential light chain, cardiac myosin regulatory light chain, and cardiac titin/connectin. Most mutations cause cardiomyopathies in an autosomal dominant manner. Interestingly, the same sarcomeric gene was found to be simultaneously responsible for different forms of cardiomyopathy.1,2 For example, many mutations in cTnT, cTnC, α-tropomyosin, α-cardiac actin, β-myosin heavy chain, and titin have been found in both HCM and primary DCM that is clearly distinguished from an end-stage …