title: Congenital heart defects are rarely caused by mutations in cardiac and smooth muscle actin genes.
abstract: 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.
  
  
  RESULTS
  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.
authors: Institute of Molecular Biology and Genetics, Federal Almazov Medical Research Centre, 2 Akkuratova Street, Saint-Petersburg 197341, Russia.
authors: Tatiana
authors: T
authors: Khodyuchenko
authors: Institute of Molecular Biology and Genetics, Federal Almazov Medical Research Centre, 2 Akkuratova Street, Saint-Petersburg 197341, Russia.
authors: Anna
authors: A
authors: Zlotina
authors: Institute of Molecular Biology and Genetics, Federal Almazov Medical Research Centre, 2 Akkuratova Street, Saint-Petersburg 197341, Russia.
authors: Tatiana
authors: T
authors: Pervunina
authors: Endovascular Surgery Department, Federal Almazov Medical Research Centre, 2 Akkuratova Street, Saint-Petersburg 197341, Russia.
authors: Dmitry
authors: D
authors: Zverev
authors: Institute of Molecular Biology and Genetics, Federal Almazov Medical Research Centre, 2 Akkuratova Street, Saint-Petersburg 197341, Russia ; St. Petersburg State University, Universitetskaya Nab. 7/9, St. Petersburg 199034, Russia.
authors: Anna
authors: A
authors: Malashicheva
authors: Institute of Molecular Biology and Genetics, Federal Almazov Medical Research Centre, 2 Akkuratova Street, Saint-Petersburg 197341, Russia ; Department of Women and Child Health, Karolinska Institute, and Centre for Molecular Medicine, 17176 Stockholm, Sweden.
authors: Anna
authors: A
authors: Kostareva
mesh_terms: D000199:Actins / Q000235:genetics*; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D004374:Ductus Arteriosus, Patent / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006344:Heart Septal Defects, Atrial / Q000235:genetics*; D006801:Humans; D008297:Male; D009130:Muscle, Smooth / Q000473:pathology*; D020125:Mutation, Missense / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: C541116:ACTA2 protein, human; C526913:ACTC1 protein, human; D000199:Actins; D004247:DNA