A novel mutation in exon 1 of GATA4 in Egyptian patients with congenital heart disease

Shaker, Olfat G.; Omran, Salwa; Sharaf, Eman F.; Hegazy, Gehan A.; Mashaly, Mohamed; Gaboon, Nagwa E. A.

doi:10.3906/sag-1605-166

Cited by 6 publications

(3 citation statements)

References 16 publications

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“…Therefore, our patients will be subjected to further molecular testing, in order to correctly assess their diagnosis. The GATA4 gene encodes a protein involved in embryogenesis and myocardial differentiation and function, and its involvement in CHD occurrence was previously reported, both in syndromic patients (in 8p23.1 duplication syndrome [18] associated with TNKS1 and SOX7 genes) as well as non-syndromic CHDs associated to modifications in the gene's exon1 [19].…”

Section: Results and Discusisonsmentioning

confidence: 92%

MLPA � first-tier Screening Assay in Newborns with Nonsyndromic Congenital Heart Disease

Moldovan¹,

Moldovan²,

Bănescu³

et al. 2020

Rev. Chim.

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Congenital heart disease(CHD) is the most frequent malformative pathology seen in newborns, with an incidence of 10/1000 births, and is considered a major cause of neonatal morbidity and mortality. About one third of congenital heart disease cases are of genetic origin, particular copy number variations being described as possible nonsyndromic and syndromic congenital heart disease causes. Here, we set out to find whether the MLPA technique could be used as a first-tier screening assay in newborns with apparently nonsyndromic CHDs, and thus to genetically confirm the CHD diagnosis. The study cohort included 60 newborns diagnosed with apparently nonsyndromic congenital heart disease, recruited for a period of 18 months. MLPA analysis was performed using the SALSA MLPA P311 and P250 kits. 10 newborns (16.67%) showed known genetically relevant copy number variations, namely three patients with 22q11.21 deletion, that were diagnosed with DiGeorge syndrome, and seven patients with a probable single exon 8p23.1 duplication that will be subjected to further molecular testing, in order to correctly assess their diagnosis. We can conclude that the screening of patients with apparently nonsyndromic congenital heart disease may lead to their early and correct diagnosis, and thus them benefitting from the detection of clinically relevant copy number variations using the MLPA technique.

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Section: Results and Discusisonsmentioning

confidence: 92%

MLPA � first-tier Screening Assay in Newborns with Nonsyndromic Congenital Heart Disease

Moldovan¹,

Moldovan²,

Bănescu³

et al. 2020

Rev. Chim.

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“…There is a lack of information on the genetic architecture (cardiogenesis genes) of CHD on the African continent even in countries with good economic standing. A case-control study in an Egyptian cohort showed a novel nonsynonymous sequence variation in GATA4 (P193H) detected in 9.1% of the study population with septal defects (Shaker et al, 2017).…”

Section: Genetic Basis Of Non-syndromic Chd: Global Populationsmentioning

confidence: 99%

Genomics and Epigenomics of Congenital Heart Defects: Expert Review and Lessons Learned in Africa

Thomford

Dzobo

Yao

et al. 2018

OMICS: A Journal of Integrative Biology

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Congenital heart defects (CHD) are structural malformations found at birth with a prevalence of 1%. The clinical trajectory of CHD is highly variable and thus in need of robust diagnostics and therapeutics. Major surgical interventions are often required for most CHDs. In Africa, despite advances in life sciences infrastructure and improving education of medical scholars, the limited clinical data suggest that CHD detection and correction are still not at par with the rest of the world. But the toll and genetics of CHDs in Africa has seldom been systematically investigated. We present an expert review on CHD with lessons learned on Africa. We found variable CHD phenotype prevalence in Africa across countries and populations. There are important gaps and paucity in genomic studies of CHD in African populations. Among the available genomic studies, the key findings in Africa were variants in GATA4 (P193H), MTHFR 677TT, and MTHFR 1298CC that were associated with atrial septal defect, ventricular septal defect (VSD), Tetralogy of Fallot (TOF), and patent ductus arteriosus phenotypes and 22q.11 deletion, which is associated with TOF. There were no data on epigenomic association of CHD in Africa, however, other studies have shown an altered expression of miR-421 and miR-1233-3p to be associated with TOF and hypermethylation of CpG islands in the promoter of SCO2 gene also been associated with TOF and VSD in children with non-syndromic CHD. These findings signal the urgent need to develop and implement genetic and genomic research on CHD to identify the hereditary and genome-environment interactions contributing to CHD. These projected studies would also offer comparisons on CHD pathophysiology between African and other populations worldwide. Genomic research on CHD in Africa should be developed in parallel with next generation technology policy research and responsible innovation frameworks that examine the social and political factors that shape the emergence and societal embedding of new technologies.

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“…GATA4 is involved in embryogenesis and in myocardial differentiation and function. Numerous studies have demonstrated that mutations in this gene have been associated with CHD [15,16]. Low GATA4 expression in embryonic cardiomyocytes can cause myocardial hypoplasia, and even abortion [17].…”

Section: Introductionmentioning

confidence: 99%

miR-208a Promotes Apoptosis in H9c2 Cardiomyocytes by Targeting GATA4

Gong¹,

Jiang²,

Qiu³

et al. 2021

Congenital Heart Disease

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Background: microRNAs are crucial for cardiovascular development and are associated with congenital heart disease (CHD). Recent studies have shown that microRNAs play a role in heart development and is closely related to CHD. The present study investigated the underlying mechanism of microRNA-208a (miR-208a) in "simple" CHD. Material and Methods: Reverse transcription-quantitative PCR (RT-qPCR) demonstrated miR-208a expression levels in children with CHD (n = 27) compared with normal controls (n = 29), in cardiomyocytes from embryo 10 (E10) to post-birth (P7) and organs in adult rats in healthy rats. Apoptosis of H9c2 cells after transfection with miR-208a detected by TUNEL assay. B-cell lymphoma (Bcl)-2, an anti-apoptotic gene, was detected by RT-qPCR, as well as Gata4. After 48h overexpression of miR-208a, GATA4 was detected via western blotting. Dual luciferase reporting system was used to identify the binding sites of miR-208a to Gata4. Results: Expression of miR-208a was upregulated in the CHD group via the control group (p < 0.01). At P7, miR-208a had the highest expression (p < 0.01), and which was highest in myocardiocytes via other organs or tissues (p < 0.01) in adult rats. The number of apoptotic cells increased significantly post-transfection with miR-208a (p < 0.01), while decreased with the miR-208a inhibitor via the control group (p < 0.01). Compared with the control group, there was no significant difference in the expression level of Bcl-2 after miR-208a overexpression (p > 0.05). The present study proved that miR-208a binds directly to the 3´-UTR of Gata4 at site 1,363-1,369 bp. Expression of GATA4 decreased after miR-208a overexpression (p < 0.01), but increased following transfection with a miR-208a inhibitor via the control group (p < 0.05). Conclusions: Our study demonstrated that miR-208a downregulates Bcl-2 by directly targeting GATA4, which may cause CHD. miR-208a may become a new biomarker or therapeutic target for CHD in the future.

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A novel mutation in exon 1 of GATA4 in Egyptian patients with congenital heart disease

Cited by 6 publications

References 16 publications

MLPA � first-tier Screening Assay in Newborns with Nonsyndromic Congenital Heart Disease

MLPA � first-tier Screening Assay in Newborns with Nonsyndromic Congenital Heart Disease

Genomics and Epigenomics of Congenital Heart Defects: Expert Review and Lessons Learned in Africa

miR-208a Promotes Apoptosis in H9c2 Cardiomyocytes by Targeting GATA4

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