Genetic test for the MYBPC3 gene mutation associated with hypertrophic cardiomyopathy (HCM) in the Ragdoll, marketed as «mutation 2» (variant R820W, c.2453C>T). HCM is the most common feline heart disease and causes thickening of the left ventricular walls, with impaired diastolic relaxation. It may be asymptomatic for years or trigger heart failure, arterial thromboembolism and sudden death. The test identifies clear, carrier and at-risk cats, and is a breeding tool complementary to (not a substitute for) echocardiography.

The Ragdoll is one of the breeds with the highest prevalence of HCM. The frequency of the R820W allele varies by country and breeding line, and there are no reliable consolidated figures at international level (limited data). Remember that part of Ragdoll HCM is not explained by this mutation.

- Many cats remain asymptomatic for years
- Heart murmur or audible gallop on examination
- Dyspnoea, tachypnoea or open-mouth breathing in advanced stages
- Exercise intolerance, lethargy and anorexia
- Occasional syncope
- Arterial thromboembolism: acute painful paralysis of the hind limbs with cold paw pads
- Sudden death

HCM was recognised as a familial disease in the Ragdoll in the years before the genomic era, with affected breeding lines in Europe and North America. In 2007, Meurs' group identified a substitution in the myosin-binding protein C gene (MYBPC3), the R820W variant, in Ragdolls with familial HCM. Later studies demonstrated incomplete penetrance and the existence of HCM cats negative for the mutation, confirming the genetic heterogeneity of the disease in the breed. Since then DNA testing has been incorporated into breeding programmes, together with annual echocardiographic screening.

- Test all breeding animals before the first mating
- Never mate two cats with the mutation: homozygotes should be withdrawn from breeding and heterozygotes should not be mated with each other
- A heterozygote may at most be mated with a cat clear of the mutation, also considering withdrawing the line
- A negative test does not exclude HCM: maintain annual echocardiographic screening of breeding animals
- Do not use for breeding cats with confirmed echocardiographic HCM, whatever their genotype

Echocardiography remains the diagnostic standard and the genetic test only stratifies risk for this specific variant. In the differential diagnosis of an HCM pattern, include hyperthyroidism, systemic hypertension and aortic stenosis, as well as other cardiomyopathies. NT-proBNP and radiography help in the approach to the dyspnoeic cat. Incomplete penetrance means that not every heterozygote should be labelled a 'heart patient'.

1. Meurs KM, Norgard MM, Ederer MM, Hendrix KP, Kittleson MD. A substitution mutation in the myosin binding protein C gene in ragdoll hypertrophic cardiomyopathy. Genomics 2007. PMID:17521870.
2. Gil-Ortuño C, Sebastián-Marcos P, Sabater-Molina M, Nicolas-Rocamora E, et al. Genetics of feline hypertrophic cardiomyopathy. Clin Genet 2020. PMID:32215921.
3. OMIA:002951-9685 Cardiomyopathy, hypertrophic, MYBPC3-related, autosomal dominant (Felis catus).