Congenital heart defects are rarely caused by mutations in cardiac and smooth muscle actin genes.

Background: Congenital heart defects (CHDs) often have genetic background due to missense mutations in cardiomyocyte-specific genes. For example, cardiac actin was shown to be involved in pathogenesis of cardiac septum defects and smooth muscle actin in pathogenesis of aortic aneurysm in combination with patent ductus arteriosus (PDA). In the present study, we further searched for mutations in human α-cardiac actin (ACTC1) and smooth muscle α-actin (ACTA2) genes as a possible cause of atrial septum defect type II (ASDII) and PDA.

Findings: Total genomic DNA was extracted from peripheral blood of 86 individuals with ASDs and 100 individuals with PDA. Coding exons and flanking intron regions of ACTC1 (NM_005159.4) and ACTA2 (NM_001613) were amplified by PCR with specific primers designed according to the corresponding gene reference sequences. PCR fragments were directly sequenced and analyzed. Sequence analysis of ACTC1 and ACTA2 did not identify any nucleotide changes that altered the coding sense of the genes. In ACTC1 gene, we were able to detect one previously described nucleotide polymorphism (rs2307493) resulting in a synonymous substitution. The frequency of this SNP was similar in the study and control group, thus excluding it from the possible disease-associated variants.

Conclusions: Our results confirmed that the mutations in ACTC1 gene are rare (at least <1%) cause of ASDII. Mutations in ACTA2 gene were not detected in patients with PDA, thus being excluded from the list of frequent PDA-associated genetic defects.