Mutations in the Cypher/ZASP gene were identified in 6% of probands with left ventricular dysfunction, suggesting they can cause dilated cardiomyopathy and left ventricular non-compaction.
Observational (n=100)
Are mutations in the Cypher/ZASP gene associated with dilated cardiomyopathy and left ventricular non-compaction?
Mutations in the Cypher/ZASP gene are present in approximately 6% of patients with left ventricular dysfunction, providing a mechanistic basis for some cases of dilated cardiomyopathy and left ventricular non-compaction.
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.
Vatta et al. (2003) conducted an observational in Dilated cardiomyopathy and left ventricular non-compaction (n=100). Cypher/ZASP gene screening was evaluated on Identification of Cypher/ZASP mutations. Mutations in the Cypher/ZASP gene were identified in 6% of probands with left ventricular dysfunction, suggesting they can cause dilated cardiomyopathy and left ventricular non-compaction.