Open Access

ARTICLE

Novel mutation of GATA4 gene in Kurdish population of Iran with nonsyndromic congenital heart septals defects

Fariborz Soheili^1,2, Zahra Jalili³, Mahtab Rahbar⁴, Zahed Khatooni¹, Amir Mashayekhi⁵, Hossein Jafari⁶

1 Cellular and Molecular Research Center, Kurdistan University of Medical Sciences, Sanandaj, IR, Iran
2 Department of Marine Biology, Faculty of Marine Sciences, Chabahar Maritime University, Chabahar, IR, Iran
3 Department of Cardiology, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, IR, Iran
4 Department of Pathology, Faculty of Medicine, Iran Medical University of Medical Science, Tehran, IR, Iran
5 Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University Tehran, IR, Iran
6 Department of Statistic and Basic Science, Chabahar Maritime University, Chabahar, IR, Iran

* Corresponding Author: Fariborz Soheili, Department of Medical Genetic, Kurdistan University of Medical Sciences, Pasdaran Street, Sanandaj, Kurdistan province, Iran, Post code: 6618634683. Email:

Congenital Heart Disease 2018, 13(2), 295-304. https://doi.org/10.1111/chd.12571

Abstract

Background: The mutations in GATA4 gene induce inherited atrial and ventricular septation defects, which is the most frequent forms of congenital heart defects (CHDs) constituting about half of all cases.
Method: We have performed High resolution melting (HRM) mutation scanning of GATA4 coding exons of nonsyndrome 100 patients as a case group including 39 atrial septal defects (ASD), 57 ventricular septal defects (VSD) and four patients with both above defects and 50 healthy individuals as a control group. Our samples are categorized according to their HRM graph. The genome sequencing has been done for 15 control samples and 25 samples of patients whose HRM analysis were similar to healthy subjects for each exon. The PolyPhen-2 and MUpro have been used to determine the causative possibility and structural stability prediction of GATA4 sequence variation.
Results: The HRM curve analysis exhibit that 21 patients and 3 normal samples have deviated curves for GATA4 coding exons. Sequencing analysis has revealed 12 nonsynonymous mutations while all of them resulted in stability structure of protein 10 of them are pathogenic and 2 of them are benign. Also we found two nucleotide deletions which one of them was novel and one new indel mutation resulting in frame shift mutation, and 4 synonymous variations or polymorphism in 6 of patients and 3 of normal individuals. Six or about 50% of these nonsynonymous mutations have not been previously reported.
Conclusion: Our results show that there is a spectrum of GATA4 mutations resulting in septal defects.

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