Cardiovascular disease modelling with induced pluripotent stem cells in three generations of a family with DiGeorge syndrome

DiGeorge syndrome (DGS), also called 22q11.2 deletion syndrome (22q11.2DS) or velocardiofacial syndrome, is the most common microdeletion syndrome with a prevalence of 1:4000 in live births and based on invasive prenatal testing; the occurrence is as high as 1:1000 in foetuses. The genetic background of the disease is a monoallelic microdeletion on chromosome 22 caused by meiotic chromosomal rearrangements due to non-allelic homologous recombination. 22q11.2 deletion is one of the most common causes of congenital heart disease and developmental delays; 64 % of patients develop congenital heart disease. The most frequent cardiac defects are interrupted aortic arch, truncus arteriosus, tetralogy of Fallot, ventricular septal defects and vascular rings. Here, we generated a hiPSC-based disease model for DGS by using cells from a family of three patients and healthy relatives as an example for modelling a genetic disease. We described the genetic differences between patients involved in this study regarding the 22q11.2 deletion. We generated cardiovascular cells from the hiPSC of DGS patients and described the phenotype between diseased and healthy cell derivatives.