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. 2020 Oct;52(3):283-287.
doi: 10.5152/eurasianjmed.2020.19237.

Absence of GATA4 Mutations in Moroccan Patients with Atrial Septal Defect (ASD) Provides Further Evidence of Limited Involvement of GATA4 in Major Congenital Heart Defects

Ihssane El Bouchikhi  1   2 , Laila Bouguenouch  1 , Fatima Zohra Moufid  1 , Khadija Belhassan  1 , Imane Samri  1 , Amal Chaouti  1 , Mohammed Iraqui Houssaïni  3 , Samir Atmani  4 , Karim Ouldim  1
Affiliations

Absence of GATA4 Mutations in Moroccan Patients with Atrial Septal Defect (ASD) Provides Further Evidence of Limited Involvement of GATA4 in Major Congenital Heart Defects

Ihssane El Bouchikhi et al. Eurasian J Med. 2020 Oct.

Abstract

Objective: Atrial septal defect (ASD) is one of the most common types of congenital heart disease (CHD). It is mainly caused by mutations of NK2 homeobox 5, GATA binding protein 4 (GATA4), and myosin heavy chain 6 in non-syndromic cases. This study aims to carry out, for the first time, the GATA4 mutation screening in a Moroccan population affected by ASD and compare the obtained mutation rate across populations.

Materials and methods: A total of 33 patients were enrolled in this study. DNAs were extracted from peripheral blood samples, and we performed PCR-sequencing for GATA4 coding regions. Sequences were analyzed by sequence alignment and functional impact prediction tools. Mutation rate comparisons were performed by R software using the appropriate statistical tests.

Results: We detected 7 variants, but no pathogenic mutation was revealed, except for Asn352= that was assessed by human splicing finder algorithms to have a potential impairing effect on the splicing mechanism. Until proven by in vitro functional studies, the current pathogenic mutation rate in our cohort seems to be 0%. Statistical comparison with previous studies from all over the world shows no significant difference. Seemingly, comparison of previous GATA4 mutation rates among tetralogy of Fallot (TOF) populations shows no significant difference.

Conclusion: The low rates of GATA4 mutations observed throughout ASD and TOF international populations may suggest a limited causality of GATA4 mutations in the main CHDs, which further confirms the co-involvement of additional genetic and/or environmental factors in the manifestation of these phenotypes.

Keywords: Atrial Septal Defect; DNA mutational analysis; genetic testing; mutation rate; tetralogy of fallot.

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Conflict of interest statement

Conflict of Interest: Authors have no conflicts of interest to declare.

Figures

Figure 1. a–d
Figure 1. a–d
(a) GATA4 domains with sites of exonic variants and (b–d) Sequencing chromatograms of detected GATA4 variants
Figure 2
Figure 2
Output of HSF algorithms prediction for Asn352= impact on splicing process
See this image and copyright information in PMC

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