Quick Search:

uzh logo
Browse by:

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-6228

Klaassen, S; Probst, S; Oechslin, E; Gerull, B; Krings, G; Schuler, P; Greutmann, M; Hürlimann, D; Yegitbasi, M; Pons, L; Gramlich, M; Drenckhahn, J D; Heuser, A; Berger, F; Jenni, R; Thierfelder, L (2008). Mutations in sarcomere protein genes in left ventricular noncompaction. Circulation, 117(22):2893-2901.

[img] PDF - Registered users only
View at publisher


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.


157 citations in Web of Science®
199 citations in Scopus®
Google Scholar™



3 downloads since deposited on 01 Dec 2008
0 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
Dewey Decimal Classification:610 Medicine & health
Date:3 June 2008
Deposited On:01 Dec 2008 15:25
Last Modified:05 Apr 2016 12:36
Publisher:Lippincott Wiliams & Wilkins
Publisher DOI:10.1161/CIRCULATIONAHA.107.746164
PubMed ID:18506004

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page