Molecular mechanisms of Ellis‑van Creveld gene variations in ventricular septal defect.

摘要: The Ellis-van Creveld (EVC) gene is associated with various congenital heart diseases. However, studies on EVC variations in ventricular septal defect (VSD) and the underlying molecular mechanisms are sparse. present study detected 11 single‑nucleotide polymorphisms (SNPs) 65 patients VSD 210 control from Chinese Han population. Of identified SNPs only c.1727G>A SNP site was positively development of (P G, also identified, which causes a leucine to valine substitution at amino acid 115 protein (p.L115V). results functional prediction indicated that c.343C>G may be pathogenic mutation. In addition, NIH3T3 mouse embryonic fibroblast cells, mutation significantly decreased cell proliferation increased apoptosis. Further investigation demonstrated overexpression reduced binding between smoothened, further downregulated activity hedgehog (Hh) signaling pathway expression downstream cyclin D1 B‑cell lymphoma 2 proteins SAG. susceptibility mechanism induced by due reduction anti‑apoptotic proliferative abilities cardiomyocytes via downregulation Hh activity. provide novel targets for diagnosis treatment VSD.