22q11 deletions and cardiac disease

Chromosome 22q11 deletions constitute one of the most frequent genetic mutations associated with congenital heart disease. The finding of abnormalities within this locus in patients with DiGeorge syndrome provided the first evidence linking conotruncal and aortic arch anomalies with 22q11.2 mutations. Once non-syndromic patients with identical cardiac defects were also found to exhibit deletions within 22q11.2, strong support was generated for the concept that either a single gene defect, or a group of genes operating together, account for isolated cases of congenital heart disease. Recent advances in the characterization of the genes which comprise this region has brought us closer to the ultimate goal of isolating candidate disease genes. The understanding of how these genes (and those genes soon to be identified) regulate biological processes will hasten progress towards insight into the mechanisms leading to specific congenital heart lesions. This knowledge will bring us closer to comprehension of the genetic basis of normal cardiovascular development.