1. AIMS OF THE STUDY
CHD occurs through heterogeneous and complex processes. Multiple genetic and molecular mechanisms, involving mutations in genes critical for cardiac morphogenesis as well as dysregulation of the post-transcriptional control, may play a crucial role.
The overall goal of this thesis was to expand the knowledge of CHD pathogenesis in order to improve the genetic counseling as well as to identify potential targets for new therapeutic approaches.
Specific aims were:
1. to investigate the presence of both somatic and germline mutations in GATA4 and NKX2.5 genes;
2. to evaluate if the presence of genetic variants in the 3’UTR of GATA4 and NKX2.5 genes can alter the binding with specific microRNAs and influence the post-transcriptional control;
3. to analyze the association between SNPs and haplotypes in the 3’UTR of the GATA4 gene and CHD risk;
4. to investigate the presence of novel rare mutations in 17 genes related to CHD by using a next generation sequencing technology in selected CHD patients.