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Science 302 (5650): 1578-1581

Copyright © 2003 by the American Association for the Advancement of Science

Mutation of MEF2A in an Inherited Disorder with Features of Coronary Artery Disease

Lejin Wang,1,2 Chun Fan,1,2 Sarah E. Topol,1 Eric J. Topol,1,3* Qing Wang1,2*

Abstract: The early genetic pathway(s) triggering the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI) remain largely unknown. Here, we describe an autosomal dominant form of CAD/MI (adCAD1) that is caused by the deletion of seven amino acids in transcription factor MEF2A. The deletion disrupts nuclear localization of MEF2A, reduces MEF2A-mediated transcription activation, and abolishes synergistic activation by MEF2A and by the transcription factor GATA-1 through a dominant-negative mechanism. The MEF2A protein demonstrates strong expression in the endothelium of coronary arteries. These results identify a pathogenic gene for a familial vascular disease with features of CAD and implicate the MEF2A signaling pathway in the pathogenesis of CAD/MI.

1 Center for Cardiovascular Genetics, Department of Cardiovascular Medicine, and Center for Molecular Genetics, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation
2 Department of Molecular Medicine
3 Department of Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA.

* To whom correspondence should be addressed. E-mail: wangq2{at} (Q.W.) and topole{at} (E.J.T.)

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