A gene mutation responsible for a devastating heart disease in cats -- which is also a leading cause of sudden death in young athletes -- has been identified by a team of researchers at the University of California, Davis; The Ohio State University; and the Baylor College of Medicine.

This is the first report of a spontaneous genetic mutation causing any type of heart disease in a cat or dog and the first to identify a mutation in a non-human species causing hypertrophic cardiomyopathy. The discovery of the mutation in Maine coon cats was reported Oct. 19 online in the journal Human Molecular Genetics.

The human form of hypertrophic cardiomyopathy was responsible for the deaths of the Boston Celtics' Reggie Lewis in 1993 and Loyola Marymount University basketball player Hank Gathers in 1990. The disease causes an excessive thickening of the muscle of the left ventricle, the lower left chamber of the heart.

"This finding paves the way for development of a screening test that will identify those Maine coon cats carrying this genetic mutation so that they can be identified before they are bred, thus reducing the incidence of the disease and, we hope, ridding this breed of the disease," said Mark Kittleson, a veterinary cardiologist at UC Davis and a co-author on the study.

"We also are hopeful that this discovery will provide a valuable model for investigators in both veterinary and human medicine who are studying the disease," he said. He noted that the findings of this study should equip scientists to further investigate the mechanism by which this mutation leads to thickening of the muscle and potentially to pursue novel treatments for the disease, based on this knowledge.

The nature of hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy occurs in one out of every 500 humans and is the most common heart disease in domestic cats. It is characterized by progressive thickening of the left ventricular myocardium (heart muscle) -- most commonly during adolescence and young adulthood in both humans and cats -- a defect that can be detected if the heart is examined using an ultrasound procedure known as echocardiography.

The disease, however, is highly variable, and in some cases ultrasound evidence is not present until much later in life. Sudden death from abnormal electrical activity in the heart can occur at any stage. At some age, the disease reaches its maximum severity, ranging from mild to severe. In cats, if the disease is severe, it causes heart failure.

When viewed at the microscopic level, hypertrophic cardiomyopathy in humans and Maine coon cats appears as poorly aligned muscle fibers. The fibers are aligned in an orderly parallel fashion in normal heart muscle but are scattered erratically in a heart affected by the disease. This abnormality is thought to interfere with the electrical activity of the heart, resulting in rapid or irregular heart rhythms.

Cats with hypertrophic cardiomyopathy often develop severe disease, which may lead to heart failure, or a blood clot in the heart's left atrium that most commonly breaks loose and lodges in the terminal aorta, resulting in acute pain and paralysis. Sudden death often occurs.

"Veterinary therapies for this condition in domestic cats cannot halt the progression of the disease," Kittleson said.

"These therapies are only able to provide limited relief when the disease is severe, so the prognosis for severely affected cats is often poor," he added. "Consequently, preventing the disease from occurring by identifying affected cats before they are bred can save a lot of heartache."

Maine coon cat colony at UC Davis

Since the early 1990s, Kittleson and colleagues, primarily Kathryn Meurs, formerly of The Ohio State University and lead author on this paper, have been studying the genetic basis of the disease in a research colony of Maine coon cats at UC Davis. Meurs is now at Washington State University.

The research project began when Marcia Munro, a private owner of a Maine coon cat with hypertrophic cardiomyopathy, notified Kittleson that she knew of several cats related to her cat that also had the disease.

The Maine coon cat is a native American longhaired breed in which, along with many other cat breeds, hypertrophic cardiomyopathy is common. The disease is most frequently diagnosed in non-purebred middle-aged cats, although it has been diagnosed in cats ranging from one to 13 years of age.

Previous research in humans with hypertrophic cardiomyopathy has identified more than 200 mutations in 11 genes involved with the production of certain muscle proteins known as sarcomeric proteins, which are responsible for the heart's contraction. It previously had been thought that a mutation in one of these genes might also lead to hypertrophic cardiomyopathy in Maine coon cats by affecting protein function or structure.

Now that one gene mutation has been identified in one cat breed, the researchers hope that the same mutation or, more likely, different mutations will be identified in other purebred cats.

The researchers evaluated 23 related Maine coon cats from a colony of this breed at UC Davis and 100 unaffected mixed-breed cats for the control group. The cats were examined with echocardiograms to determine the presence and severity of hypertrophic cardiomyopathy. Sixteen of the 23 Maine coon cats were found to have the disease.

Hunt for the gene mutation

Meurs and colleague Peter Reiser of the College of Dentistry at The Ohio State University found that Maine coon cats affected with hypertrophic cardiomyopathy had a marked reduction in one of the sarcomeric proteins, known as cardiac myosin binding protein C. Because of this abnormality, the researchers decided to target this protein for analysis.

In the cats with hypertrophic cardiomyopathy, they discovered a change in one of the pairs of chemical compounds, called nucleotides, which make up DNA. Where the normal gene carried the nucleotide guanine, the mutated gene substituted the nucleotide cytosine. This, in turn, changed the amino acid in the region from alanine to proline. This change was not found in any of the non-affected Maine coon cats or in cats from the control group. The gene that encodes for the targeted protein is one of the most frequent genes to have a mutation in human families affected by hypertrophic cardiomyopathy.

Symptoms of the disease in the affected cats ranged from moderate to severe. Six of the 16 cats with hypertrophic cardiomyopathy carried two copies of the mutated gene, while the other 10 carried one copy. Those with two copies of the mutated gene mostly died suddenly at a young age, while three of the 10 cats with only one copy lived beyond eight years of age.

In addition to Kittleson, Meurs, Reiser and Munro, collaborators on this study include Ximena Sanchez, Ryan David, Neil Bowles and Jeffrey Towbin of the Baylor College of Medicine, and Judith Kittleson and Kristin MacDonald at UC Davis.

Funding for the study was provided by the Winn Feline Foundation and its Ricky Fund, the Center for Companion Animal Health at UC Davis, and various private donors.