Novel genes with a role in deadly heart defects identified

By identifying genes in patients and testing their effects in fruit flies, researchers from Sanford Burnham Prebys have found new genes that contribute to hypoplastic left heart syndrome (HLHS), a rare, life-threatening heart disease that occurs in infants. The findings, published in the journal eLife, bring scientists one step closer to unraveling the biology of this complex disease.

In babies with HLHS, the left side of the heart (left ventricle) is underdeveloped and unable to pump oxygenated blood to the rest of the body. Though rare, HLHS is extremely dangerous—it is nearly always fatal without multiple open-heart surgeries.

Genetics is thought to be a major driver of HLHS, but the specific genes involved have remained a mystery. To look for genes that contribute to HLHS, the researchers sequenced the genomes of 183 people with HLHS and their parents, including a family in which the parents were genetically related to each other. Focusing on this family helped the researchers narrow their search to a few key genes.

To test whether the genes they identified could be contributing to HLHS, the researchers performed genetic experiments on fruit fly hearts that are built with genes similar to those found in human hearts. They found that blocking the activity of these genes in flies interfered with their heart’s ability to contract, leading to significant heart defects.

Reference: Mitochondrial MICOS complex genes, implicated in hypoplastic left heart syndrome, maintain cardiac contractility and actomyosin integrity, eLife, DOI 10.7554/eLife.83385.