Researchers have identified a genetic mutation linked to hypertrophic cardiomyopathy (HCM) and sudden death in golden retrievers, marking the first time such a variant has been found in dogs. The study, published in Circulation: Genomic and Precision Medicine, could improve early detection and prevention of the disease in golden retrievers and enhance understanding of HCM in humans.
HCM is a heart disease that leads to thickening of the left ventricular muscle, impairing the heart’s ability to pump oxygenated blood. It can result in abnormal clotting, irregular rhythms, or heart failure. While HCM is most common in humans and cats—affecting about one in 500 people and one in seven cats—it was previously thought to be rare among dogs.
The research team analyzed whole genome sequences from three related golden retriever puppies who died suddenly from cardiac causes before age two. Their genetic data were compared with those of family members, more than 2,500 unrelated dogs from various breeds, as well as wolves and coyotes. Through bioinformatic analysis, they identified a single genetic variant in the Cardiac Troponin-I gene (TNNI3).
“In humans, TNNI3 mutations are associated with juvenile HCM and sudden death,” said Victor Rivas, DVM student and Ph.D. graduate at North Carolina State University and first author of the study. “This is the first genetic variant to explain HCM outside of humans and cats. And while it is specific to golden retrievers, it’s the first variant to be described in any dog breed.”
The study determined that this mutation is autosomal recessive—two copies are required for disease manifestation—so both parents must carry the gene for offspring to be affected. In this case, both parent dogs appeared healthy but were carriers.
The findings may help prevent further spread of HCM within golden retrievers by enabling genotype testing for breeders interested in screening their animals for carrier status.
“The positive news is that by collaborating with the golden retriever community we may be able to ensure that HCM remains a very rare disease in dogs,” Rivas said. “Additionally, the case similarities in humans and golden retrievers with these TNNI3 variants is remarkable and could lead to translational health studies that can shape our understanding of the disease mechanisms and ultimately benefit humans with similar mutations.”
Other contributors from North Carolina State University included Michael Vandewege, Ronald Li, Sandra Losa, Meghan Leber, Panchan Sitthicharoenchai, and Joshua Stern; additional collaborators came from University of Calgary, Pulse Veterinary Cardiology, and Highview Animal Clinic.
The full citation for the study is: “Novel Cardiac Troponin-I Missense Variant (c.593C>T) Is Associated With Familial Hypertrophic Cardiomyopathy in Golden Retrievers,” DOI:10.1161/CIRCGEN.125.005096.
