Congenital heart disease (CHD) is a heart defect that a baby is born with. It is the most common type of birth defect, affecting 1 in 100 babies worldwide, with about 12 affected babies born each day in the UK. Untreated, more than half of these will die. Such defects occur because something goes wrong as the baby’s heart forms in the womb. This can be because of faulty genes inherited from the parents, or it can be caused by environmental factors affecting the mother during pregnancy.
Most research in this area over the past 20 years has focused on understanding the genetic causes of CHD. However, even though the latest genome sequencing technologies have identified mutations in over 100 genes that can cause CHD, still only 20-30% of cases can be explained genetics alone.
Scientists at the Victor Chang Cardiac Research Institute in Sydney, Australia and DPAG's Duncan Sparrow have been studying how environmental factors might exacerbate the effects of genetic mutations to cause CHD. They have now shown that during normal pregnancy, mouse embryos lacking one copy of a gene associated with human CHD are completely normal, but when they are exposed to reduced oxygen levels in utero, their hearts form abnormally. This causes reduced heart rates and the sudden death of the embryos. They show that this is due to a normal cellular response to low oxygen levels acting pathologically to switch off the function of the remaining copy of the CHD-associated gene.
This work, partly funded by two British Heart Foundation grants, provides new evidence that some cases of CHD may be caused by the combination of genetic and environmental factors that each by itself does not cause a birth defect, but only do so when combined. This research may be applicable to prospective mothers with a family history of CHD, suggesting that it would be advisable for them to avoid known environmental risk factors for CHD.
Read the full paper published in Development here.
A summary is also available in the journal's "research highlights" section.