A Pilot Study of Multiplex Ligation-Dependent Probe Amplification Evaluation of Copy Number Variations in Romanian Children with Congenital Heart Defects.

Congenital heart defects (CHDs) have had an increasing prevalence over the last decades, being one of the most common congenital defects. Their etiopathogenesis is multifactorial in origin. About 10-15% of all CHD can be attributed to copy number variations (CNVs), a type of submicroscopic structural genetic alterations. The aim of this study was to evaluate the involvement of CNVs in the development of congenital heart defects. We performed a cohort study investigating the presence of CNVs in the 22q11.2 region and GATA4, TBX5, NKX2-5, BMP4, and CRELD1 genes in patients with syndromic and isolated CHDs. A total of 56 patients were included in the study, half of them (28 subjects) being classified as syndromic. The most common heart defect in our study population was ventricular septal defect (VSD) at 39.28%. There were no statistically significant differences between the two groups in terms of CHD-type distribution, demographical, and clinical features, with the exceptions of birth length, weight, and length at the time of blood sampling, that were significantly lower in the syndromic group. Through multiplex ligation-dependent probe amplification (MLPA) analysis, we found two heterozygous deletions in the 22q11.2 region, both in patients from the syndromic group. No CNVs involving GATA4, NKX2-5, TBX5, BMP4, and CRELD1 genes were identified in our study. We conclude that the MLPA assay may be used as a first genetic test in patients with syndromic CHD and that the 22q11.2 region may be included in the panels used for screening these patients.

Genetic Alterations of Transcription Factors and Signaling Molecules Involved in the Development of Congenital Heart Defects-A Narrative Review.

Congenital heart defects (CHD) are the most common congenital abnormality, with an overall global birth prevalence of 9.41 per 1000 live births. The etiology of CHDs is complex and still poorly understood. Environmental factors account for about 10% of all cases, while the rest are likely explained by a genetic component that is still under intense research. Transcription factors and signaling molecules are promising candidates for studies regarding the genetic burden of CHDs. The present narrative review provides an overview of the current knowledge regarding some of the genetic mechanisms involved in the embryological development of the cardiovascular system. In addition, we reviewed the association between the genetic variation in transcription factors and signaling molecules involved in heart development, including TBX5, GATA4, NKX2-5 and CRELD1, and congenital heart defects, providing insight into the complex pathogenesis of this heterogeneous group of diseases. Further research is needed in order to uncover their downstream targets and the complex network of interactions with non-genetic risk factors for a better molecular-phenotype correlation.