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Understanding the Genetic and Non-genetic Interconnections in the Aetiology of Isolated Congenital Heart Disease: An Updated Review: Part 1

  • Congenital Heart Disease (RA Krasuski and G Fleming, Section Editors)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Congenital heart disease (CHD) is the most frequently occurring birth defect. Majority of the earlier reviews focussed on the association of genetic factors with CHD. A few epidemiological studies provide convincing evidence for environmental factors in the causation of CHD. Although the multifactorial theory of gene-environment interaction is the prevailing explanation, explicit understanding of the biological mechanism(s) involved, remains obscure. Nonetheless, integration of all the information into one platform would enable us to better understand the collective risk implicated in CHD development.

Recent Findings

Great strides in novel genomic technologies namely, massive parallel sequencing, whole exome sequencing, multiomics studies supported by system-biology have greatly improved our understanding of the aetiology of CHD. Molecular genetic studies reveal that cardiac specific gene variants in transcription factors or signalling molecules, or structural proteins could cause CHD. Additionally, non-hereditary contributors such as exposure to teratogens, maternal nutrition, parental age and lifestyle factors also contribute to induce CHD. Moreover, DNA methylation and non-coding RNA are also correlated with CHD.

Summary

Here, we inform that a complex combination of genetic, environmental and epigenetic factors interact to interfere with morphogenetic processes of cardiac development leading to CHD. It is important, not only to identify individual genetic and non-inherited risk factors but also to recognize which factors interact mutually, causing cardiac defects.

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Data Availability

No datasets were generated or analysed during the current study.

Abbreviations

AD:

Autosomal dominant

AR:

Autosomal recessive

AS:

Aortic stenosis

ASD:

Atrial septal defect

AVSD:

Atrioventricular septal defect

BAV:

Bicuspid aortic valve

CNVs:

Copy number variations

CoA:

Coarctation of aorta

DCM:

Dilated cardiomyopathy

DILV:

Double inlet left ventricle

DORV:

Double outlet right ventricle

EA:

Ebstein’s anomaly

HCM:

Hypertrophic cardiomyopathy

HLHS:

Hypoplastic left heart syndrome

HOS:

Holt-Oram syndrome

IAA:

Interrupted aortic arch

LVOTO:

Left ventricular outflow tract obstruction

NGS:

Next-generation sequencing

OFT:

Outflow tract

PDA:

Patent ductus arteriosus

PS:

Pulmonary stenosis

PTA:

Persistent truncus arteriosus

RVOTO:

Right ventricular outflow tract obstruction

SNVs:

Single nucleotide variants

SVAS:

Supravalvular aortic stenosis

TA:

Tricuspid atresia

TAPVR:

Total anomalous pulmonary venous return

TGA:

Transposition of great arteries

ToF:

Tetralogy of Fallot

VSD:

Ventricular septal defect

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Acknowledgements

We are very grateful to Prof. Rajiva Raman, Department of Zoology, BHU, Varanasi, India for critically reviewing the manuscript, his valuable suggestions and grammatical corrections.

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  1. Cytogenetics Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Uttar Pradesh, Varanasi, 221005, India

    Jyoti Maddhesiya & Bhagyalaxmi Mohapatra

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Jyoti Maddhesiya performed the literature search and prepared the original draft including all figures and tables and reference formatting. Dr. Bhagyalaxmi Mohapatra sketched the outline for the article, critically supervised and revised the manuscript at every single step. Both authors read and approved the final manuscript.

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Maddhesiya, J., Mohapatra, B. Understanding the Genetic and Non-genetic Interconnections in the Aetiology of Isolated Congenital Heart Disease: An Updated Review: Part 1. Curr Cardiol Rep 26, 147–165 (2024). https://doi.org/10.1007/s11886-024-02022-9

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