Genetic impact of copy number variations on congenital heart defects: Current insights and future directions

Abstract

Congenital heart defects (CHDs) are the most prevalent congenital abnormalities, and they are commonly associated with genetic alterations, namely copy number variants. CNVs, which are duplications or deletions of DNA sequences, can disrupt gene regulation, impact dosage-sensitive genes, and cause loss-of-function mutations, all of which can interfere with heart development. CNVs cause genomic instability by changing essential genes, which plays an important role in the pathophysiology of CHDs. Detecting these variants is critical for better understanding the genetic causes of these abnormalities and improving patient outcomes. Advanced genetic testing tools aid in detecting CNVs linked to CHDs. Multiplex Ligation-Dependent Probe Amplification (MLPA), High-throughput Ligation-Dependent Probe Amplification (HLPA), Whole Exome Sequencing (WES), Chromosomal Microarray Analysis (CMA), and CNV-specific sequencing (CNV-seq) have all greatly improved the detection of these variants. Furthermore, whole genome sequencing (WGS) has emerged as a potent method for detecting CNVs on a wide scale, allowing for earlier diagnosis and more effective treatment planning. Therefore, this review focuses on the rising significance of CNV research in congenital heart defects, emphasizing on how genetic differences might lead to improved diagnostic and treatment options. By combining genomic technologies, researchers and clinicians can gain a better understanding of the function of CNVs in CHDs, opening the door for personalised therapy.

Keywords

• Copy number variation
• Genomic instability
• Multiplex ligation-dependent probe amplification (MLPA)
• Chromosomal microarray analysis (CMA)
• Whole exome sequencing (WES)
• CNV-specific sequencing (CNV-seq)