Identification of New Genes in Congenital Heart Defects

Abstract

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease, occurring in 1 in 3000 live births. TOF is a combination of four heart defects that affect normal blood flow. Shone’s Syndrome is another rare congenital heart disease consisting of left-sided obstructive heart lesions. Although the diagnosis of both diseases is confirmed by clinical evaluation and physical examination, their pathogenesis is unknown. This research aimed to identify and characterize new genetic variants in hereditary cardiac diseases, specifically Tetralogy of Fallot and Shone’s Syndrome. Exome sequencing identified 20 nucleotide variants in different genes among TOF patients from the United Arab Emirates and Saudi Arabia. Two different families were analyzed for TOF and Shone’s Syndrome. It was hypothesized that the probands in each family would express variants for the genes of interest. For the family affected by TOF, TRIM74 (exon 3) and KMT2C (exons 21 and 33) were analyzed. For the family affected by Shone’s Syndrome, IFT80 (exon 19) was analyzed. No association was found between TOF and the genes TRIM74 and KMT2C. The results of IFT80 seem to confirm an association with Shone’s Syndrome. To confirm the pathogenicity of the variant, functional studies need to be performed.