Novel Point Mutations of CITED2 Gene Are Associated with Non-familial Congenital Heart Disease (CHD) in Sporadic Pediatric Patients Sima Dianatpour 1 & Mehri Khatami 1 & Mohammad Mehdi Heidari 1 & Mehdi Hadadzadeh 2 Received: 16 May 2019 /Accepted: 25 August 2019/ # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract CITED2 is a cardiac transcription factor that plays a critical role in cardiac development. Gene mutations in CITED2 lead to a series of cardiac malformations and congenital heart defects (CHD). Congenital heart disease generally refers to defects in the heart’s structure or function and often seen in many forms such as ventricular septal defects (VSDs), atrial septal defects (ASDs), and tetralogy of Fallot (TOF). However, the mechanisms involved in these mutations are poorly understood. The aim of the present study was to evaluate the mutations of the CITED2 gene in pediatric patients with congenital heart defects. We studied the potential impact of sequence variations of the CITED2 gene in a cohort of 150 patients with non- familial CHD and 98 control individuals by polymerase chain reaction-single-stranded con- formation polymorphism (PCR-SSCP) and subsequently direct sequencing. We identified seven novel CITED2 nucleotide changes. Four of these alterations were found in the coding region (c.716insG, c.389A>G, c.450G>C and c.512-538del27) and were only seen in our patients, and not detected in the control group. These mutations are leading to changes in the amino acid sequence in the position of p.Gly236fs, p.Asn125Ser, p.Gln145His, and p.Ser170- Gly178del, respectively. Other variations are located in the 5′UTR region of the gene (c.- 43C>T, c.-64C>T and c.-90A>G). CITED2 gene mutations in control subjects were not observed. Our Bioinformatics assay results showed that these novel mutations alter the RNA folding, protein structure, and, therefore, probable effect on the protein function and may play a significant role in the development of congenital heart diseases. Keywords Congenital heart disease . CITED2 . Mutation . PCR-SSCP Applied Biochemistry and Biotechnology https://doi.org/10.1007/s12010-019-03125-8 * Mehri Khatami m.khatami@yazd.ac.ir 1 Department of Biology, Faculty of Science, Yazd University, Yazd, Iran 2 Department of Cardiac Surgery, Afshar Hospital, Shahid Sadoughi University of Medical Sciences, Yazd, Iran