Researchers from the Francis Crick Institute and University College London have identified a gene that causes heart defects in Down syndrome.
Published in Science Translational Medicine, researchers studied human Down syndrome foetal and embryonic hearts from a mouse model of Down syndrome.
Affecting around one in 800 new births, Down syndrome is caused by an extra third copy of chromosome 21.
Approximately 50% of babies born with Down syndrome are affected by heart defects, including a failure of the heart to separate into four chambers, leaving a hole in the heart.
To understand which extra 230 genes on chromosome 21 are responsible for heart defects, researchers used genetic mapping to identify a gene on human chromosome 21 known as Dyrk1a.
Previously linked to cognitive impairment and facial changes in Down syndrome, Dyrk1a, which encodes for an enzyme known as DYRK1A, causes heart defects when present in three copies in the mouse model of Down syndrome.
After adding an extra copy of Dyrk1a, the gene activity required for cell division in the developing heart was turned down, along with the function of the mitochondria, which produces energy for cells.
Researchers suggest that these changes are correlated with a failure to correctly separate the chambers of the heart.
Additionally, the team tested a DYRK1A inhibitor on pregnant mice with pups, which model the heart defects in Down syndrome. When inhibited, the genetic changes were partially reversed and the heart defects in the pups were less severe.
Researchers hope that the DYRK1A inhibitor could have a similar effect on the human heart later in pregnancy or potentially after birth.
Furthermore, the team also found another, unknown gene involved in the origin of heart defects, as the Dyrk1a gene alone was not sufficient in the mouse models.
Eva Lana-Elola, principal laboratory research scientist at the Crick, said: “We’re now aiming to understand which of the other genes on this extra chromosome are involved.”
