Genes effects may cause congenital heart defects: Study

The role of genes in congenital heart defects is more complex than previously thought with new research finding that the overall risk is determined by a combination of gene effects on both inside and outside of the heart itself.

Congenital heart defect (CHD) is a problem in the structure of the heart that is present at birth and are a leading cause of birth defect-related deaths.

Normal heart formation depends on interactions of multiple types of cells that collaborate in precise times and places throughout development to build the heart's intricate structures.

To figure out how these interactions can go awry, researchers at the University of California, at Irvine, in the US, studied atrial septal defects (ASDs, a common type of heart defect) in a mouse model.

They studied the developmental disorder Cornelia de Lange Syndrome (CdLS) -- a very rare genetic disorder present from birth, but not always diagnosed at birth.

Most cases of Cornelia de Lange Syndrome are caused by mutations that inactivate a single copy of Nipbl -- a gene that directs the expression of many hundreds of other genes in tissues throughout the body.

Just as people with Cornelia de Lange Syndrome have a high incidence of heart defects, 30 per cent of mice that harbour similar Nipbl mutations exhibit atrial septal defects, the researchers said.

Using genetically modified mouse models, they then selectively introduced or removed Nipbl mutations in different tissues during embryonic development.

The findings showed that no Nipbl deficiency in any single tissue -- including the tissue that forms the heart itself -- could single-handedly account for the development of atrial septal defects.

Rather, the development of heart defects was determined by interactions between heart-forming tissues and the rest of the body.

In fact, Nipbl deficiency in some tissues even seemed to protect against the development of atrial septal defects, in certain situations, the researchers explained.

"The study results show that heart defects such as ASDs occur when the heart does not grow quickly enough to meet the demands of the developing body -- in other words, that heart size and body size must be coordinated for the heart to develop without defects," said Anne Calof, Professor at University of California, at Irvine.

"This is the first genetic demonstration that major risk factors for heart defects are likely to lie outside of the heart itself," Calof added, in the paper published in the journal PLOS Biology.

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