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J Am Coll Cardiol. 2003 Dec 3;42(11):2014-27.

Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction.

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  • 1Department of Pediatrics (Cardiology), Baylor College of Medicine, Houston, Texas, USA.

Abstract

OBJECTIVES:

We evaluated the role of Cypher/ZASP in the pathogenesis of dilated cardiomyopathy (DCM) with or without isolated non-compaction of the left ventricular myocardium (INLVM).

BACKGROUND:

Dilated cardiomyopathy, characterized by left ventricular dilation and systolic dysfunction with signs of heart failure, is genetically transmitted in 30% to 40% of cases. Genetic heterogeneity has been identified with mutations in multiple cytoskeletal and sarcomeric genes causing the phenotype. In addition, INLVM with a hypertrophic dilated left ventricle, ventricular dysfunction, and deep trabeculations, is also inherited, and the genes identified to date differ from those causing DCM. Cypher/ZASP is a newly identified gene encoding a protein that is a component of the Z-line in both skeletal and cardiac muscle.

METHODS:

Diagnosis of DCM was performed by echocardiogram, electrocardiogram, and physical examination. In addition, levels of the muscular isoform of creatine kinase were measured to evaluate for skeletal muscle involvement. Cypher/ZASP was screened by denaturing high performance liquid chromatography (DHPLC) and direct deoxyribonucleic acid sequencing.

RESULTS:

We identified and screened 100 probands with left ventricular dysfunction. Five mutations in six probands (6% of cases) were identified in patients with familial or sporadic DCM or INLVM. In vitro studies showed cytoskeleton disarray in cells transfected with mutated Cypher/ZASP.

CONCLUSIONS:

These data suggest that mutated Cypher/ZASP can cause DCM and INLVM and identify a mechanistic basis.

PMID:
14662268
[PubMed - indexed for MEDLINE]
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