Pathogenicity analysis of E۲۳۴A mutation in the CITED۲ gene in Ventricular septal defects (VSD)

Backgrounds: Ventricular septal defects (VSD) are congenital defects in the dividing wallbetween the two ventricles. The ventricular septum consists of an upper membranous region andunder muscular region. The membranous anomalies are common and in most cases, surgery isneeded, but small muscular defects often close themselves. These defects cause blood to leakfrom the left ventricle to the right ventricle and ultimately it leads to pulmonary hypertension andmultiple complications.Materials and Methods: In this study, we are looking for a dangerous mutation in a generelated to the important transcription factor, CITED۲, in these defects. We found the missenseand likely pathogenic mutation E۲۳۴A at National Center for Biotechnology Information (NCBI)database. In this mutation, a hydrophilic amino acid, Glutamate, was exchanged into ahydrophobic amino acid, Alanine, at position ۲۳۴. We analyzed this mutation at SortingIntolerant from Tolerant (SIFT), Polymorphism Phenotyping (PolyPhen) and Protein VariationEffect Analyzer (PROVEAN) online bioinformatics databases.Results: The result of analysis at PROVEAN database showed that this mutation is deleterious.Research on the SIFT database showed that substitution at position ۲۳۴ from E to A is predictedto affect protein function with a score of ۰.۰۰. The result of analysis at PolyPhen showed thatthis mutation is predicted to be probably damaging with a score of ۰.۹۹۹.Conclusion: According to the results of this study, this mutation most probably disrupts thefunction and stability of this protein and plays a role in causing these defects. However, moreresearch is needed to prove conclusively that this mutation is pathogenic.

کلیدواژه ها:

VSD ، CITED۲ ، SIFT ، PROVEAN ، PolyPhen