Mutations in Cypher/ZASP in patients with dilated cardiomyopathy and left ventricular non-compaction.
J Am Coll Cardiol
; 42(11): 2014-27, 2003 Dec 03.
Article
em En
| MEDLINE
| ID: mdl-14662268
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.
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Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Dilatada
/
Proteínas de Transporte
/
Disfunção Ventricular Esquerda
/
Proteínas de Homeodomínio
/
Ventrículos do Coração
/
Proteínas Musculares
/
Mutação
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2003
Tipo de documento:
Article