Gene behind heart defects in Down syndrome identified

Researchers at the Francis Crick Institute and UCL have identified a gene that causes heart defects in Down syndrome, a condition that results from an additional copy of chromosome 21. Reducing the overactivity of this gene partially reversed these defects in mice, setting the scene for potential future therapies for heart conditions in people with Down syndrome. Down syndrome affects around one in 800 new births and is caused by an extra third copy of chromosome 21. About half of babies born with Down syndrome have heart defects, such as a failure of the heart to separate into four chambers, leaving a “hole in the heart.” If the heart defects are very serious, high-risk surgery might be needed soon after birth and people often require ongoing monitoring of the heart for the rest of their life. Therefore, better treatment options are needed and this must be guided by knowledge of which of the extra 230 genes on chromosome 21 are responsible for the heart defects. The Science Translational Medicine says a team at Crick and UCL studied Down syndrome using genetic mapping and identified a gene on human chromosome 21 called Dyrk1a, which causes heart defects when present in three copies in the mouse model of Down syndrome. This gene has previously been linked to cognitive impairment and facial changes in Down syndrome, but its role in heart development was not known. An extra copy of Dyrk1a turned down the activity of genes required for cell division in the developing heart and the function of the mitochondria, which produce energy for the cells. These changes correlated with a failure to correctly separate the chambers of the heart. The team found that while Dyrk1a is required in three copies to cause heart defects in mice, it was not sufficient alone. Thus, another unknown gene must also be involved in the origin of heart defects in Down syndrome. The team is currently searching for this second gene. This research forms part of the lab’s overall goal to understand the genetics behind all aspects of Down syndrome. The researchers worked to test the DYRK1A inhibitor, and are now testing the drug in a clinical trial for cognitive disorders associated with Down syndrome and Alzheimer’s disease.

Source: Science Translational Medicine