Genomic and bioinformatics analysis of nucleotide changes in the coding regions of the CCDC103 gene in patients with Tetralogy of Fallot (TOF): A type of Congenital Heart Defects

Background and Aims: Tetralogy of Fallot (TOF) is one of infants' most common types of complex congenital heart defects (CHD). Several molecular mechanisms may play a role in its development, such as mutations in cardiac gene network components, cardiac gene regulatory pathways, dysfunction of cilia-expressing genes, and dysfunction of genes determining the left and right axis of the heart. The present study aimed to investigate the nucleotide changes of the CCDC103 gene and its relationship with CHD of the TOF type. Materials and Methods: The present work was conducted for the first time in Iran as a case-control study on 85 children with TOF. The control group involved 56 healthy children without a family history of heart disorders. Touchdown polymerase chain reaction (PCR) and Sanger sequencing were used to evaluate point mutations in the CCDC103 gene. Moreover, bioinformatics databases were employed to predict the impact of nucleotide changes on protein structure and function. Results: A total of five heterozygous single nucleotide changes were detected in this gene (three missense mutations: p.S115R, p.C191R, p.M201V, a synonymous change without amino acid change, and a change in the 3'-UTR region). In addition, bioinformatics results predicted that p.C191R mutation is pathogenic and harmful. Conclusion: The results indicated that in addition to the genes known in the pathogenesis of TOF, changes in the CCDC103 gene in the ciliary signaling pathway can play a role in causing heart defects.