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High throughput mutation screening of cardiac transcription factor GATA4 among Tanzania children with congenital heart diseases

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Abstract

Congenital heart disorders (CHDs) are common, estimated to affect 8 out of every 1000 live births, and they are associated with high mortality and morbidity. It is still unknown what causes CHDs. In the pathophysiology of CHD, environmental and inherited factors are both involved. The zinc-finger transcription factor GATA4 is crucial for the early stages of heart morphogenesis. Early expression of GATA4 in the pro-cardiogenic splanchnic mesoderm is necessary for the creation of pre-epicardium during cardiac development. Additionally, it controls the expression of the Wnt 11 gene, which controls early cardiogenesis. Congenital heart disorders are thought to be brought on by GATA4 mutations. The role of GATA4 mutations in the occurrence of congenital cardiac disorders in our environment is not well understood. Case–control GATA4 mutation analysis was performed to shed light on the etiology of sporadic non-syndromic congenital cardiac disorders. Using high-resolution melting assays and sequencing analysis, we have screened exons 7 and 2 of GATA4, which are regarded as molecular hot spots in patients with sporadic congenital heart diseases. In addition, we sequenced GATA4 exon 7, which comprises crucial regulatory components involved in polyadenylation, nuclear transport, translation, and messenger RNA degradation. We have taken into account non-inherited risk factors that are also connected to the pathophysiology of congenital heart disorders, such as folic acid, alcohol, gestational age, birth weight, and maternal age. We have identified missense insertion, silent substitution, and missense substitution of the GATA4 gene in phenotypes, namely; tetralogy of Fallot, ventricular septal defects, and atrial septal defects.

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Data availability and materials

Patient data and participant blood samples were obtained at JKCI, and all the references in this manuscript were cited from PubMed and Google Scholar. We used Endnote software version 8 for data management and referencing.

Abbreviations

ASD:

Atrial septal defect

VSD:

Ventral septal defects

AVSD:

Atrial ventral septal defects

DORV:

Double outlet right ventricle

TGV:

Transposition of greater vessels

TOF:

Tetralogy of fallot

JKCI:

Jakaya Kikwete Cardiac Institute

CHDs:

Congenital heart diseases

DNA:

Deoxyribonucleic Acid

DBS:

Dry blood sample

GATA4:

GATA 4 binding protein gene

MUHAS:

Muhimbili University of Health and Allied Sciences

HRMA:

High resolution melting assays

PAH:

Pulmonary arterial hypertension

PCR:

Polymerase chain reaction

aOR:

Adjusted odd ratios

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Acknowledgements

We thank the University of Shandong, the University of Muhimbili, and the Jakaya Kikwete Cardiac Institute for providing the facilities and guidance required for effective writing and submitting the article for publication.

Funding

The corresponding author received funds for writing this manuscript from the Chinese Government Scholarship (CSC).

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Authors and Affiliations

  1. School of Basic Sciences, Shandong University, 44 Wenhua Xi Road, Jinan, 250012, Shandong, China

    Emmanuel Suluba

  2. Department of Biochemistry, School of Medicine, Muhimbili University of Health and Allied Sciences, P.O.BOX 65001, Dar-es-salaam, Tanzania

    James Masaganya, Erasto Mbugi & Teddy Mselle

  3. School Basic Medical Sciences, Department of Anatomy and Embryology, Shandong University, Jinan, 250012, Shandong, China

    Emmanuel Suluba, Wenjia Liang & Liu Shuwei

  4. Cheeloo College of Medicine, Muhimbili University of Health and Allied Sciences, Shandong University, 44Wenhua Xi Road, Jinan, 250012, Shandong, China

    Emmanuel Suluba, Wenjia Liang & Liu Shuwei

  5. School of Veterinary Medicine, Sokoine University of Agriculture, P.O.BOX 3000, Dar-es-salaam, Tanzania

    Mwinyi Masala & Benezeth M. Mutayoba

  6. Jakaya Kikwete Cardiac Institute, Research and Publication, P.O.BOX 65141, Dar-es-salaam, Tanzania

    Naizihijwa Majani & Sulende Kubhoja

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  1. Emmanuel Suluba
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Contributions

All the authors participated in the whole process of writing the manuscript. Emmanuel Suluba (ES) and Weinjia Liang; concept, drafting the manuscript, and manuscript writing; James Masaganya (JM); literature review and manuscript writing; Mwinyi Masala (MM); molecular methods review; Naizihijwa Majani (NM); clinical method review; Erasto Mbugi (EM) and Teddy Mselle (TM); manuscript collections and supervision; Benezeth M. Mutayoba (BM); provide technical support, supervision on molecular techniques, Liu Shuwei (LS), provide guidelines, drafting, manuscript corrections and supervision。

Corresponding author

Correspondence to Emmanuel Suluba.

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All authors consented to publish.

Ethical approval and consent to participate

Ethical clearance for conducting this study was obtained from the Muhimbili University Institutional Review Board (MUHAS-IRB) (Ref.No.DA.282/298/01.C/MUHAS-REC-06–2021-666). Permission to collect data was obtained from the Director of the Jakaya Kikwete Cardiac Institute research and publication committee (Ref: AB.123/307/01E/16). Participants were informed about the aim of the study and their rights, including the right to withdraw from the study at any stage without losing any benefit from the study. We asked the participants to provide consent to allow them and their children to participate in this study.

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Suluba, E., Masaganya, J., Liang, W. et al. High throughput mutation screening of cardiac transcription factor GATA4 among Tanzania children with congenital heart diseases. Nucleus 66, 11–30 (2023). https://doi.org/10.1007/s13237-022-00414-2

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