Lack of MEF2A mutations in coronary artery disease
Li Weng, … , Ruth McPherson, Len A. Pennacchio
Li Weng, … , Ruth McPherson, Len A. Pennacchio
Published April 1, 2005
Citation Information: J Clin Invest. 2005;115(4):1016-1020. https://doi.org/10.1172/JCI24186.
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Article Cardiology

Lack of MEF2A mutations in coronary artery disease

Abstract

Mutations in MEF2A have been implicated in an autosomal dominant form of coronary artery disease (adCAD1). In this study we sought to determine whether severe mutations in MEF2A might also explain sporadic cases of coronary artery disease (CAD). To do this, we resequenced the coding sequence and splice sites of MEF2A in approximately 300 patients with premature CAD and failed to find causative mutations in the CAD cohort. However, we did identify the 21-bp MEF2A coding sequence deletion originally implicated in adCAD1 in 1 of 300 elderly control subjects without CAD. Further screening of approximately 1,500 additional individuals without CAD revealed 2 more subjects with the MEF2A 21-bp deletion. Genotyping of 19 family members of the 3 probands with the 21-bp deletion in MEF2A revealed that the mutation did not cosegregate with early CAD. These studies support that MEF2A mutations are not a common cause of CAD in white people and argue strongly against a role for the MEF2A 21-bp deletion in autosomal dominant CAD.

Authors

Li Weng, Nihan Kavaslar, Anna Ustaszewska, Heather Doelle, Wendy Schackwitz, Sybil Hébert, Jonathan C. Cohen, Ruth McPherson, Len A. Pennacchio

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Sequence of the 21-bp deletion region of MEF2A. The PCR products from co...
Sequence of the 21-bp deletion region of MEF2A. The PCR products from common and deletion alleles were separated by 3% agarose gel, purified, and cloned for sequencing analysis. The 21-bp deletion was identified in 3 independent control subjects. The 7 deleted amino acids are depicted with a dashed-line box. Haplotype analysis of all 3 subjects with the 21-bp deletion as well as approximately 370 control subjects indicates that this variant resides on a common haplotype, consistent with the deletion arising through a single ancestral founding event (data not shown).