In a large study of congenital heart defects in 22q11.2DS, comprising 1053 cases, it is suggested that although the LCR A–B region was considered the critical region for the 22q11.2 phenotype and especially for heart defects, the presence of congenital cardiac defects in patients with LCR B–D and LCR C–D deletions (20–30% of cases) highlights the importance of the LCR C–D region in normal cardiac development, and proposes haploinsufficiency of the CRKL gene as the main factor involved in conotruncal heart defects [35]. The gene discussed is CRKL; the disease is congenital heart disease.