Pathogenicity analysis of G۲۹۷C in GATA۴ gene in non-syndromic Tetralogy of fallot (TOF)

Backgrounds: Tetralogy of Fallot (TOF), composed of four (tetralogy) congenitalabnormalities, is the most common type of congenital heart disease (CHD) and could becontrolled by specific transcription factor genes. TOF accounts for ۷% to ۱۰% of congenitaldefects, affecting males and females equally and occurring in ۳ to ۵ of every ۱۰۰۰۰ live births.So genetic variation studies in the GATA۴ gene, a transcription factor for heart development isconsidered important in TOF cases. Mutation in this gene has been associated with cardiac septaldefects.Materials and Methods: In this study. We found a G۲۹۷C mutation of the GATA۴ gene inNCBI. This mutation converts glycine, a hydrophobic amino acid into cysteine, a hydrophilicamino acid. We assessed the effect of this mutation on polymorphism and phenotyping(PolyPhen) and protein functional (SIFT).Results: Our results showed that this substitution at position ۲۹۷ from G to C is predicted toaffect protein function with a score of ۰.۰۰ (deleterious) (SIFT). The PolyPhen score predicts thepossible impact of an amino acid substitution on the structure and function, this mutant ispredicted to be probably damaging with a score of ۱.۰۰. The wild-type residue is glycine, themost flexible of all residues. This flexibility might be necessary for the protein’s function.Mutation of this glycine can abolish this function.Conclusion: The Results of this study predicted that its mutation could be damaging and it wasconsidered potentially pathologic. However, further researches are necessary to clarify this.

کلیدواژه ها:

Tetralogy of Fallot ، congenital heart disease ، mutation ، SIFT ، PolyPhen