Abstract

Background: Congenital heart disease (CHD) is the most common birth defect and affects nearly 1% of newborns. The aetiology 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 very little is known about the impact of DNA copy number changes in non-syndromic CHD.

Method: A sub-megabase resolution array comparative genome hybridisation (CGH) screen was carried out on 105 patients with CHD as the sole abnormality at the time of diagnosis.

Results: There were 18 chromosomal changes detected, which do not coincide with common 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 submicroscopic 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 counselling and should pave the way for the elucidation of the pathogenetic mechanisms underlying CHD.