Background: Congenital heart disease (CHD) is the most frequent birth defect and affects nearly 1% of newborns. The etiology of CHD is largely unknown and only a small percentage can be assigned to environmental risk factors such as maternal diseases or exposure to mutagenic agents during pregnancy. Chromosomal imbalances have been identified in many forms of syndromic CHD, but next to nothing is known about the impact of DNA copy number changes in non-syndromic CHD.
Methods and Results: Here we present a sub-megabase resolution array CGH screen of 105 patients with CHD as the sole abnormality at the time of diagnosis. We have detected 18 chromosomal changes that do not coincide with frequent DNA copy number variants, including one de novo deletion, two de novo duplications and eight familial copy number variations; one deletion and seven duplications.
Conclusions: Our data show that sub-microscopic deletions and duplications play an important role in the aetiology of this condition, either as direct causes or as genetic risk factors for CHD. These findings have immediate consequences for genetic counseling and should pave the way for the elucidation of pathogenetic mechanisms underlying CHD.