Sarcomere mutations in cardiogenesis and ventricular noncompaction.
Ventricular noncompaction is a form of cardiomyopathy where increased trabeculation is present frequently affecting the left ventricle and resembling an embryonic state of heart development. Clinically, left ventricular noncompaction may manifest as congestive heart failure, arrhythmias, and/or thromboembolic events. There are multiple genes linked to noncompaction, but recently, sarcomere gene mutations were found in both familial and sporadic cases of noncompaction. The association of noncompaction with sarcomere mutations supports the classification of ventricular noncompaction as cardiomyopathy and raises interesting questions regarding the continuum of hypertrophic cardiomyopathy, dilated cardiomyopathy, and noncompaction. The mutational spectrum of sarcomere genes in these disorders highlights the importance of the MYH7 gene encoding beta-myosin heavy chain and ACTC1 encoding the cardiac actin gene. Intriguingly, these mutations also share a low but definitive incidence of congenital heart malformations including septal defects. These human genetic findings support that normal myocardial and sarcomere function are required for proper compaction and septation and that these mutations also portend a high risk of developing heart failure in later life.
McNally
Elizabeth
E
Department of Medicine, Section of Cardiology, The University of Chicago, Chicago, IL 60637, USA. emcnally@uchicago.edu
Dellefave
Lisa
L
D000199:Actins / Q000235:genetics; D001145:Arrhythmias, Cardiac / Q000235:genetics; D024722:Cardiac Myosins / Q000235:genetics; D009202:Cardiomyopathies / Q000209:etiology / Q000235:genetics*; D006330:Heart Defects, Congenital / Q000235:genetics; D006333:Heart Failure / Q000235:genetics; D006343:Heart Septal Defects / Q000235:genetics; D006352:Heart Ventricles / Q000002:abnormalities*; D006801:Humans; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics; D012518:Sarcomeres / Q000737:chemistry / Q000235:genetics*; D013923:Thromboembolism / Q000235:genetics
C526913:ACTC1 protein, human; D000199:Actins; C501641:MYH7 protein, human; D024722:Cardiac Myosins; D018995:Myosin Heavy Chains