Mutations in sarcomere protein genes in left ventricular noncompaction

Item Type:	Article
Title:	Mutations in sarcomere protein genes in left ventricular noncompaction
Creators Name:	Klaassen, S. and Probst, S. and Oechslin, E. and Gerull, B. and Krings, G. and Schuler, P. and Greutmann, M. and Huerlimann, D. and Yegitbasi, M. and Pons, L. and Gramlich, M. and Drenckhahn, J.D. and Heuser, A. and Berger, F. and Jenni, R. and Thierfelder, L.
Abstract:	BACKGROUND: Left ventricular noncompaction constitutes a primary cardiomyopathy characterized by a severely thickened, 2-layered myocardium, numerous prominent trabeculations, and deep intertrabecular recesses. The genetic basis of this cardiomyopathy is still largely unresolved. We speculated that mutations in sarcomere protein genes known to cause hypertrophic cardiomyopathy and dilated cardiomyopathy may be associated with left ventricular noncompaction. METHODS AND RESULTS: Mutational analysis in a cohort of 63 unrelated adult probands with left ventricular noncompaction and no other congenital heart anomalies was performed by denaturing high-performance liquid chromatography analysis and direct DNA sequencing of 6 genes encoding sarcomere proteins. Heterozygous mutations were identified in 11 of 63 samples in genes encoding beta-myosin heavy chain (MYH7), alpha-cardiac actin (ACTC), and cardiac troponin T (TNNT2). Nine distinct mutations, 7 of them in MYH7, 1 in ACTC, and 1 in TNNT2, were found. Clinical evaluations demonstrated familial disease in 6 of 11 probands with sarcomere gene mutations. MYH7 mutations segregated with the disease in 4 autosomal dominant LVNC kindreds. Six of the MYH7 mutations were novel, and 1 encodes a splice-site mutation, a relatively unique finding for MYH7 mutations. Modified residues in beta-myosin heavy chain were located mainly within the ATP binding site. CONCLUSIONS: We conclude that left ventricular noncompaction is within the diverse spectrum of cardiac morphologies triggered by sarcomere protein gene defects. Our findings support the hypothesis that there is a shared molecular etiology of different cardiomyopathic phenotypes.
Keywords:	Cardiomyopathy, Genetics, Heart Failure, Remodeling, Myocardium
Source:	Circulation
ISSN:	0009-7322
Publisher:	American Heart Association
Volume:	117
Number:	22
Page Range:	2893-2901
Date:	3 June 2008
Official Publication:	https://doi.org/10.1161/CIRCULATIONAHA.107.746164
PubMed:	View item in PubMed

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