Pathogenic analysis of R۴۵۶C mutation in the GATA۶ gene in atrial septal defect (ASD)

Backgrounds: Atrial septal defect (ASD) is an autosomal disorder characterized by formation ofa hole in the atrial septal, which may vary in size and severity. It accounts for ۵-۱۰% of allcongenital heart defects (CHD). GATA۶ is a member of the GATA transcription factor family,which is located on chromosome ۱۸ and plays an important role in the development of the heart.Mutations in this gene are associated with several congenital heart defects including ASD.Materials and Methods: In this study, we identified from the National Center forBiotechnology Information (NCBI) database the pathogenic mutation that altered a positively Rgroup amino acid, Arginine, at position ۴۵۶, to a polar uncharged R group amino acid, Cysteine.This missense mutation is located in the DNA binding region of GATA۶ protein.Results: Our results showed that R۴۵۶C mutation is probably damaging with a score of ۱.۰۰۰ atPolymorphism Phenotyping (PolyPhen) database and a score of -۷.۷۳۳ at Provean database,which is predicted to be deleterious. Also at Sorting Intolerant From Tolerant (SIFT) database,substitution at position ۴۵۶ from R to C is predicted to affect protein function with a score of۰.۰۰.Conclusion: According to the results of this study, the R۴۵۶C mutation altered the function ofcorresponding protein and predicted that it could possibly be damaging. However, furtherinvestigations are necessary to clarify this.

کلیدواژه ها:

ASD ، GATA۶ ، Mutation ، R۴۵۶C ، Database