title: Mutation of MEF2A in an inherited disorder with features of coronary artery disease.
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.
authors.affiliation: Center for Cardiovascular Genetics, Department of Cardiovascular Medicine, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH 44195, USA.
authors.forename: Lejin
authors.initials: L
authors.lastname: Wang
authors.forename: Chun
authors.initials: C
authors.lastname: Fan
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Topol
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Topol
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001158:Arteries / Q000378:metabolism; D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics* / Q000378:metabolism; D003331:Coronary Vessels / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D019281:Dimerization; D004730:Endothelium, Vascular / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D005260:Female; D005455:Fluorescent Antibody Technique; D050982:GATA1 Transcription Factor; D015870:Gene Expression; D005799:Genes, Dominant; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D009203:Myocardial Infarction / Q000235:genetics* / Q000378:metabolism; D018006:Myogenic Regulatory Factors; D010375:Pedigree; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D012307:Risk Factors; D017384:Sequence Deletion; D015398:Signal Transduction; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; C494690:Gata1 protein, rat; D005819:Genetic Markers; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; D018006:Myogenic Regulatory Factors; D014157:Transcription Factors