MAINE COON HYPERTROPHIC CARDIOMYOPATHY

A familial form of hypertrophic cardiomyopathy in the Maine Coon cat was reported by Dr. Mark Kittleson at the University of California, Davis, in 1999.⁵ Breeding studies demonstrated that it was an autosomal dominant trait. Autosomal dominant traits should have the following criteria: males and females generally are affected equally, every affected individual should have at least one affected parent, and the trait generally is observed in every generation (Figure 39-1). Affected animals may carry the genetic mutation on one or both copies of the gene. If the mutation is on both copies of the gene (one inherited from each parent), they are called homozygous for the mutation and will pass one copy of the mutation to all of their offspring. They are defined as heterozygous if they have one gene with the mutation and one normal gene. Heterozygous cats have a 50 per cent chance of passing on the genetic mutation to their offspring. This does not mean that 50 per cent of a litter of kittens will have the mutation, but rather that each kitten has a 50 per cent chance of having the mutation. The litter may actually have from zero to 100 per cent of kittens born with the mutation.

Figure 39-1 Example of a family of cats with an autosomal dominant mode of inheritance of hypertrophic cardiomyopathy. Male cats are depicted as a square, females as a circle. Affected cats are indicated by solid black symbols and unaffected cats are indicated by solid white symbols. Autosomal dominant traits should have equal (or almost equal) numbers of affected males and females, every affected individual should have at least one affected parent, and the trait generally is observed in every generation.

An additional important, but poorly understood, aspect of the inheritance of hypertrophic cardiomyopathy in the Maine Coon cat is that hypertrophic cardiomyopathy appears to be inherited with incomplete penetrance. This means that cats who have the mutation will have different degrees of disease severity depending on the “penetrance” of the trait in that animal. Even within the same litter, two siblings may have the same mutation; however, one sibling may show a more severe form than the other, and some cats may never actually show a clinical form of the disease.

In the Maine Coon cat a genetic mutation has been identified in the myosin binding protein C (MYBPC3) gene.² Myosin binding protein C is a cardiac sarcomeric protein involved in cardiac contraction. It is the second most commonly mutated gene responsible for the human form of the disease.⁶ In the Maine Coon cat the mutation is a single base pair change from a guanine to a cytosine in the 31st codon of the gene. The mutation changes the highly conserved amino acid that is produced from alanine to proline, a large amino acid with a ring. Additionally, the alteration of the amino acid is predicted to change the structure of myosin binding protein C in this region, and alters the ability of the cardiac protein to interact with other contractile proteins.

Homozygous (two copies of the mutated gene) Maine Coon cats are thought to typically, but not always, develop a more severe form of hypertrophic cardiomyopathy and may show clinical signs before 4 years of age.² Heterozygous (one copy of the mutated gene) cats may develop the disease at a later age and have milder signs. As mentioned a small percentage of cats with the mutation may never show clinical signs of the disease, as a result of incomplete penetrance. Genetic modifiers that affect the expression and penetrance of the disease are likely, but have yet to be determined.

The Maine Coon mutation appears to be quite breed-specific. It is unlikely to be associated with hypertrophic cardiomyopathy in other breeds of cats unless they are closely related to the Maine Coon breed.