Genetic basis of Hypertrophic Cardiomyopathy in Ragdoll cats - is caused by a breed-specific autosomal dominant mutation in the MYBPC3 gene. The mutation is a single base pair substitution known as R820W, which alters the cardiac myosin binding protein C essential for normal heart muscle function. Cats inherit two copies of this gene (one from each parent), and those with two copies of the mutation (homozygous) are at high risk of developing severe HCM, typically between 1 to 2 years of age. Cats with one copy (heterozygous) may not show clinical signs and often live a normal lifespan. The mutation exhibits incomplete penetrance, meaning not all cats carrying the gene develop the disease.
Pathophysiology - The R820W mutation in the MYBPC3 gene disrupts the structure and function of the myosin binding protein C in cardiomyocytes. This impairment leads to abnormal thickening (hypertrophy) of the left ventricular heart muscle, reducing chamber compliance and impairing heart function. The thickened heart muscle compromises diastolic function, which can result in heart failure and increased risk of sudden cardiac death. The disease severity is generally greater in homozygous cats, with clinical signs usually appearing early in life.
Complications - Affected Ragdolls, especially those homozygous for the mutation, may develop: Progressive thickening of the left ventricular wall. Impaired heart function leading to congestive heart failure. Arrhythmias and increased risk of sudden cardiac death, often at a young age (1-2 years). Reduced exercise tolerance, lethargy, and potential thrombosis from impaired blood flow. Shortened lifespan compared to heterozygous or normal cats.
Why This Matters to Breeders and Vets - Genetic Testing: DNA tests can identify Ragdoll cats carrying one or two copies of the R820W mutation, enabling informed breeding choices to prevent producing homozygous affected kittens. Breeding Strategy: Breeding heterozygous cats to normal (non-mutant) cats is recommended to avoid homozygous offspring, which are at the highest risk of severe HCM. Veterinary Management: Early identification of mutation carriers helps veterinarians monitor and manage cardiac health proactively, including cardiac ultrasound screening. Welfare: Preventing homozygous affected kittens reduces suffering and premature death due to this fatal heart disease. Prevalence: Approximately 13–30% of Ragdolls carry the mutation, demonstrating the importance of testing within the breed.
Summary - Ragdoll Hypertrophic Cardiomyopathy is caused by an autosomal dominant R820W mutation in the MYBPC3 gene, leading to abnormal thickening of the heart muscle and increased risk of sudden cardiac death. Cats homozygous for the mutation typically develop severe disease at a young age, while heterozygous cats are less likely to be affected. Genetic testing and careful breeding practices are essential for reducing the prevalence and impact of HCM in Ragdoll populations, enabling early diagnosis and better management to improve feline health and welfare.
