Researchers from North Carolina State University and the University of Arizona have identified a gene associated with a dilated cardiomyopathy, a common cause of heart disease in Doberman pinschers.

Since dilated cardiomyopathy affects the heart muscle’s ability to contract, it leads to congestive heart failure,  with poor prognosis. Humans with dilated cardiomyopathy have the same grim prognosis, despite existing medical therapies that could help treat clinical signs,  heart transplants are currently the only effective treatment.

Kate Meurs, the Associate Dean at NC State’s College of Veterinary Medicine is the lead author of a paper describing the work.

“The severity of this disease means that Doberman breeders and owners are very interested in both preventing it within the population and finding life-extending treatments,” says Dr. Meurs,” “If we could find a cause, perhaps we could develop better treatments that would not only benefit dogs, but extend human lives as well.”

Previous research by Dr. Meurs had discovered that a mutation in the pyruvate dehydrogenase kinase 4 (PDK4) gene could cause dilated cardiomyopathy in Dobermans; however, that mutation ended up being associated with a relatively small number of cases. When Meurs encountered a family of Doberman pinschers with dilated cardiomyopathy and without the PDK4 variant, she wanted to find the genetic cause of their disease.

Meurs and her colleagues performed whole genome sequencing on the Doberman family and analyzed their cardiac myofibers, or bands of heart muscle, under an electron microscope. The team discovered that another gene, called titin, was the culprit.

“For humans with dilated cardiomyopathy, a titin mutation is the most common cause,” Meurs says. “This gene is responsible for producing one of the largest proteins in both people and dogs, and is involved in enabling skeletal and cardiac muscle to contract. This mutation causes cardiac myofibers to stretch out so that the heart muscle cannot do its job properly.”

While titin’s involvement with dilated cardiomyopathy isn’t a new discovery, finding a mutation in the same gene in Doberman pinschers and humans opens up new avenues for possible treatments.

“We now know that the majority of Doberman and human cases of dilated cardiomyopathy are caused by a mutation in titin, which means that not only can breeders now have a reliable test for their dogs, but also that we can begin intervention earlier,” Meurs says. “This means we can now truly test the effectiveness of potential life-extending therapies on these animals.

 Read more:

A missense variant in the titin gene in Doberman pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death