Investigation of Genetic Causes of Familial Non-Syndromic Congenital Heart Disease Using Next Generation Sequencing Technique

The new therapeutic cardiac surgery opportunities for patients with congenital heart disease (CHD) as the most common type of birth defects has led to a remarkable growth in life expectancy and consequently elevated the risk for disease related genes being transmitted to the offsprings. Familial non-syndromic CHD occurs as a genetically heterogeneous disease, associated with mutations in numerous developmental genes -the most fundamental ones are transcription factors- (e.g. NKX2–5, GATA4 and NOTCH1). However, the CHD key genetic factors have remained mostly puzzling, and the assumption is that in more than 80% of CHD patients nounderlying mutation is identified. CHD gene discovery was greatly improved by means of direct sequencing of whole-genome and Exome commonly named Next Generation Sequencing (NGS). These technologies can uncover pathogenic variants in genetically heterogeneous diseases such as CHD. Once there is definite familial recurrence or parental consanguinity, the probability of monogenic foundation of the disease is high and Exome sequencing has been the most promising way in recognizing the causative homozygous mutations. The main challenge in NGS technique is the interpretation of the variants. There has been designed a targeted panel for sequencing of the coding regions of formerly implicated 57 genes in autosomal dominant CHD. Several studies using targeted CHD panel could identify pathogenic variants in fewer than half of their families. While the diagnostic effectiveness of CHD gene panels looks powerful in ascertaining familial forms of CHD, additional in depth research is essential in order to design a regional and specific gene panel for clinical practices. In CHD familial/hereditary cases, disease genes and/or loci recognition will assist the genetic counseling procedure for CHD families and prenatal diagnosis options. Understanding the genetic basis of such conditions and how they influence cardiac networks is decisive for therapeutic options.