How one genetic error can affect both the heart and the brain

In medicine, we tend to think of diseases organ by organ. 

A cardiologist focuses on the heart, a neurologist on the brain, and a psychiatrist on the mind. Each specialist sees their part of the picture. 

In biology, however, the lines are not always so clear.

Some conditions affect more than one organ

Some genetic conditions affect more than one organ, sometimes in very different ways and at different stages of life. 

Researchers call these multi-system disorders: conditions where a single genetic change can disrupt the development or function of multiple organs.

One example attracting growing attention involves children with severe neurodevelopmental conditions, such as intellectual disability or developmental delay. 

Many of these children also have problems with their heart. The overlap is well documented, but the biological reasons behind it remained unclear for a long time.

New research is beginning to reveal that the answer may lie deep in our DNA.

A shared genetic blueprint

Large genetic studies have shown that children with both serious brain-related conditions and heart defects often carry a single, spontaneous mutation that was not inherited from either parent. 

Researchers call this a de novo variant.

Sometimes these mutations appear in genes that guide the development of multiple organs. These genes are active during the earliest stages of embryonic development, when both the heart and the brain are forming.

If one of these genes is broken, both organs can be affected – sometimes in different ways and at different stages of development.

“A gene might be active in the heart during early weeks of pregnancy and then switch on in the brain at the later stage of pregnancy. If that gene is broken, both organs can be affected during their most critical growth periods,” says Novin Balafkan.

He is associate professor at the University of Bergen and a researcher at Haukeland University Hospital.

From individual genes to shared mechanisms

Balafkan and his colleagues studied how genes linked to neurodevelopmental disorders affect brain cells.

These genes do very different things. Some help control when other genes are switched on, while others help nerve cells communicate.

But even with these differences, they ended up causing very similar problems. 

The biggest issues showed up in excitatory neurons and early-stage brain cells, including a shared disruption in how the cells produce energy.

“This is a crucial finding. It means we don't need to understand every single gene on its own. Instead, we can group genes by the type of damage they cause and focus on the shared mechanism that ties them together,” says Balafkan.

Switch off one gene at a time

To understand the biological link between brain and heart in these children, Balafkan has started a new research project called CONVERGE.

Using human stem cells, the team uses CRISPR gene-editing technology to switch off one gene at a time. They then track how the same mutation affects cells as they develop into both heart and brain tissue.

This approach helps the researchers connect two problems that are often treated separately.

“If a genetic change affects the heart, could it also warn us about brain development, or the other way around?” asks Balafkan.

Their goal is to build a detailed map of how these shared genes affect both organs, moving the field from knowing which genes are involved to understanding what they actually do.

A step towards precision medicine

Balafkan explains that there are hundreds of mutations linked to neurodevelopmental and cardiac conditions. 

"Developing a treatment for each one is not realistic. But if many of them disrupt the same cellular pathways, it may be possible to target those shared mechanisms instead," he says. 

That would mean treating the root cause of both heart and brain problems, rather than seeing them as separate conditions.

"That would be a real step toward precision medicine,” says Balafkan.

 Reference:

Garcia et al. Transcriptomic and phenotypic convergence of neurodevelopmental disorder risk genes in vitro and in vivo, Nature Neuroscience, 2026. DOI: 10.1038/s41593-026-02247-7

About the research

The work was carried out in the Brennand Lab at Yale University with support from the Trond Mohn Research Foundation.

The CONVERGE research project at the Bergen Center for Medical Stem Cell Research is funded by a four-year grant from the Research Council of Norway.

This content is paid for and presented by the University of Bergen

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