Research Links Gene to Rare, Fatal Childhood Heart Disease
Researchers have identified a key gene that influences a rare and often fatal heart muscle disease present from birth, paving the way for new research models and potential insights into other mitochondrial disorders.
A team from the Keck School of Medicine of USC has discovered that the PCBP1 gene influences AARS2-related cardiomyopathy, a rare heart muscle disease caused by inherited mutations in the AARS2 gene. The condition is often fatal within the first year of life, and no treatment currently exists.
The study, funded in part by the National Institutes of Health and published in Nature Cardiovascular Research, found that switching off PCBP1 in mice and lab-grown human heart cells reproduces key disease features, including the disruption of mitochondrial function.
Key Findings
PCBP1 helps control how the non-mutated AARS2 gene functions in heart cells. When PCBP1 is missing, genetic messages from AARS2 are processed incorrectly.
This leads to two critical problems:
- Disrupted mitochondrial activity and reduced cellular energy.
- The activation of stress signals in heart cells, which causes further damage.
The research successfully produced a mouse model of the condition, which the team says should make it significantly easier to study the disease's mechanisms and test potential interventions.
Broader Implications
The findings may extend beyond this specific cardiomyopathy. According to the researchers, the work could have relevance for other rare diseases affecting the heart, brain, and other organs that involve mitochondrial problems.
"We think what we found in the heart can apply to many of these organs, because the root cause—mitochondrial dysfunction—is the same," stated the study's lead author.
Research Team & Funding
The study was led by Yao Wei Lu, PhD, assistant professor of medicine at the Keck School of Medicine of USC. Collaborators included researchers from the University of South Florida, Boston Children's Hospital and Harvard Medical School, University of Rochester Medical Center, and University of North Carolina at Chapel Hill, among other institutions.
Funding was provided by:
- The National Institutes of Health
- The Additional Ventures Single Ventricle Research Fund
- The Robert E. and May R. Wright Foundation
- American Heart Association Awards
- The Hastings Foundation