Genetic basis of Hypertrophic Cardiomyopathy in Maine Coon cats - is primarily associated with a breed-specific mutation in the MYBPC3 gene, which encodes the cardiac myosin binding protein C (cMyBP-C). The key mutation is a single base pair substitution (c.91G>C) resulting in the amino acid change p.A31P (alanine to proline at position 31). This mutation disrupts the protein structure, affecting normal heart muscle development and function. The inheritance pattern is autosomal dominant with incomplete penetrance, meaning cats with one copy of the mutation (heterozygotes) may or may not develop the disease, while cats with two copies (homozygotes) typically develop moderate to severe cardiac disease. About 30% of Maine Coons carry this mutation.
Pathophysiology - The defective MYBPC3 protein impairs the structure and function of the sarcomere in heart muscle cells, leading to abnormal thickening (hypertrophy) of the left ventricular wall. This thickening causes decreased heart chamber compliance and impaired diastolic function, which can progress to heart failure. The disease progresses variably: some cats develop symptoms early while others remain asymptomatic for years. HCM increases the risk of sudden cardiac death, especially in cats homozygous for the mutation.
Complications - Progressive thickening of the heart muscle (left ventricular hypertrophy). Diastolic dysfunction leading to heart failure. Arrhythmias and sudden cardiac death, often before 4 years of age in homozygous cats. Decreased exercise tolerance and lethargy. Possible thromboembolism from impaired cardiac function.
Why This Matters to Breeders and Vets - Genetic Testing: Identifying cats with one or two copies of the MYBPC3 mutation allows breeders to make informed decisions and avoid breeding two carriers, which can produce offspring with severe HCM. Disease Management: Veterinarians can monitor cats with the mutation for early signs of cardiac disease and provide timely interventions. Breeding Strategy: Since about 30% of Maine Coons carry the mutation and heterozygotes may remain healthy, it is generally advised to breed heterozygous cats to mutation-negative cats and avoid homozygous breeding. Welfare Impact: Early detection and proper breeding strategies reduce the prevalence of the disease and improve the overall health and longevity of the breed.
Summary - Maine Coon Hypertrophic Cardiomyopathy is caused by an autosomal dominant mutation (p.A31P) in the MYBPC3 gene, leading to abnormal heart muscle thickening and increased risk of sudden cardiac death. The disease shows incomplete penetrance, with more severe outcomes in cats carrying two copies of the mutation. Genetic testing is crucial for breeders and veterinarians to identify carriers, manage the condition early, and make informed breeding decisions to reduce disease incidence and enhance feline welfare.
