DGCR6 at the proximal part of the DiGeorge critical region is involved in conotruncal heart defects

Cardiac anomaly is one of the hallmarks of DiGeorge syndrome (DGS), observed in approximately 80% of patients. It often shows a characteristic morphology, termed as conotruncal heart defects. In many cases showing only the conotruncal heart defect, deletion of 22q11.2 region cannot be detected by fluorescence in situ hybridization (FISH), which is used to detect deletion in DGS. We investigated the presence of genomic aberrations in six patients with congenital conotruncal heart defects, who show no deletion at 22q11.2 in an initial screening by FISH. In these patients, no abnormalities were identified in the coding region of the TBX1 gene, one of the key genes responsible for the phenotype of DGS. However, when copy number alteration was analyzed by high-resolution array analysis, a small deletion or duplication in the proximal end of DiGeorge critical region was detected in two patients. The affected region contains the DGCR6 and PRODH genes. DGCR6 has been reported to affect the expression of the TBX1 gene. Our results suggest that altered dosage of gene(s) other than TBX1, possibly DGCR6, may also be responsible for the development of conotruncal heart defects observed in patients with DGS and, in particular, in those with stand-alone conotruncal heart defects. Researchers in Japan have linked a new gene to the characteristic heart defects associated with DiGeorge syndrome. This genetic disorder is caused by the deletion of a small piece of chromosome 22 that contains around 40 genes. One of these genes, TBX1, was thought to be mainly responsible for the congenital heart problems experienced by people with DiGeorge syndrome, but some patients who only have cardiovascular anomalies show no mutations or deletions in TBX1. Mariko Eguchi and colleagues from Ehime University Graduate School of Medicine studied the genetics of six such unrelated individuals. Two of the six patients had a small deletion or duplication in the genetic region involved in DiGeorge syndrome. The region contains only two coding genes, one of which, DGCR6, was deemed the most likely culprit because it may control TBX1expression.