Alternative titles; symbols
DO: 3393;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 15q26.3 | {Coronary artery disease, autosomal dominant, 1} | 608320 | Autosomal dominant | 3 | MEF2A | 600660 |
A number sign (#) is used with this entry because a form of autosomal dominant coronary artery disease with myocardial infarction (ADCAD1) may be related to mutation in the MEF2A gene (600660). Another form of autosomal dominant coronary artery disease (ADCAD2; 610947) is related to mutation in the LRP6 gene (603507).
Coronary artery disease (CAD) and its most important complication, acute myocardial infarction (MI), are leading causes of death and disability in the developed world. Multiple risk factors for CAD/MI have been identified, including family history, hypertension, hypercholesterolemia, obesity, smoking, and diabetes. Several genomewide scans of affected sib pairs have identified susceptibility loci for CAD, e.g., 607339 and 300464.
Wang et al. (2003) identified a large family with 13 patients with an autosomal dominant pattern of CAD. Multiple risk factors including dyslipidemia, hypertension, and cigarette smoking were present in some family members. Nine of the 13 patients developed acute MI. Five patients had required percutaneous coronary angioplasty, and 4 underwent coronary artery bypass surgery. Wang et al. (2003) performed a genomewide scan in this family and identified linkage with marker D15S120, with a lod score of 4.19 at theta = 0.0. These data mapped an autosomal dominant CAD/MI locus to chromosome 15q26, a locus which Wang et al. (2003) designated ADCAD1.
In all affected members of the large family with autosomal dominant CAD studied by them, Wang et al. (2003) found a 21-bp deletion in exon 11 of the MEF2A gene (600660.0001). The deleted 7 amino acids are conserved among MEF2A proteins in human, mouse, pig, and Chamek spider monkey. This 7-amino acid segment is also located in the conserved C-terminal region common to MEF2A and MEF2C (600662), a location that is important for nuclear localization of these 2 proteins.
Bhagavatula et al. (2004) identified 3 mutations in exon 7 of the MEF2A gene (600660.0002-600660.0004) in 4 (1.93%) of 207 coronary artery disease/myocardial infarction (CAD/MI) patients. No mutations were detected in 191 controls. The mutations were clustered within or close to the major transcription activation domain of MEF2A and resulted in loss of function of transcriptional activation activity. Loss-of-function mutations resulted in a less severe phenotype than that of the dominant-negative 21-bp deletion.
Weng et al. (2005) analyzed the coding sequence and splice sites of the MEF2A gene in 300 patients with coronary artery disease and found no causative mutations. However, they identified the 21-bp deletion in the MEF2A coding sequence in 1 of 300 elderly controls and in 2 of approximately 1,500 additional individuals without CAD who were subsequently screened. Genotyping of 19 family members of the 3 unrelated controls with the 21-bp deletion revealed that the mutation did not cosegregate with early CAD; 3 elderly individuals with the deletion had no evidence of premature CAD, and 2 individuals with premature CAD did not have the mutation. Weng et al. (2005) concluded that MEF2A mutations are not a common cause of CAD in Caucasians and argued against a role for the MEF2A 21-bp deletion in autosomal dominant CAD.
Bhagavatula, M. R. K., Fan, C., Shen, G.-Q., Cassano, J., Plow, E. F., Topol, E. J., Wang, Q. Transcription factor MEF2A mutations in patients with coronary artery disease. Hum. Molec. Genet. 13: 3181-3188, 2004. [PubMed: 15496429] [Full Text: https://doi.org/10.1093/hmg/ddh329]
Wang, L., Fan, C., Topol, S. E., Topol, E. J., Wang, Q. Mutation of MEF2A in an inherited disorder with features of coronary artery disease. Science 302: 1578-1581, 2003. [PubMed: 14645853] [Full Text: https://doi.org/10.1126/science.1088477]
Weng, L., Kavaslar, N., Ustaszewska, A., Doelle, H., Schackwitz, W., Hebert, S., Cohen, J. C., McPherson, R., Pennacchio, L. A. Lack of MEF2A mutations in coronary artery disease. J. Clin. Invest. 115: 1016-1020, 2005. [PubMed: 15841183] [Full Text: https://doi.org/10.1172/JCI24186]