HCM - hypertrophic cardiomyopathy

Primary HCM is one of the most common reasons of sudden heart failure not only in cats even in humans. The estimated incidence in humans is 1 case of 500; 60% of all cases are familial occurrence.

HCM is clinically very heterogeneous heart disease, which occurs in pure-bred cats as well as in conventional crosses. The disease manifestation starts at any age, in extreme cases from 6 months to a high age. Breed inclination for primary HCM is in Maine Coon cats, ragdoll, as well as domestic cats. Middle-aged males are affected more often than other males and females.

In HCM, primary strengthening (hypertrophy) of the left cardiac ventricle wall and the cardiac septum occurs. The cardiac wall reinforcement may be occured thanks to other diseases - that called secondary HCM. Secondary HCM is most often a result of high blood pressure (eg. during renal disease) or some hormonal diseases like hyperthyroidism (increasing of thyroid hormones).
Mutations in several genes coding sarcomere proteins have been identified, for example mutations in MYBPC3 gene (myosin binding protein C) were found. Mutations in sarcomere proteins genes may lead to the HCM phenotype development, due to influencing of sarcomere proteins structure and function. Although mutations have been identified, pathogenic HCM process has not been explored yet. HCM symptoms, that may accompany the disease, can be breath shortness, low physical activity from reduced mobility to legs paralysis, appetite decrease, cough, syncopes, heart arrhythmia and cardiac murmur of different intensity. The disease manifestation starts at any age. Clinical diagnosis is possible through heart sonography examination.

Currently, there is a genetic test for Maine Coon cats and ragdoll cats available. Test proves presence or absence of mutations in MYBPC3 gene. These mutations are inherited as an autosomal dominant trait. Incomplete penetrance of the disease was described in heterozygotes (Longer et al. 2013).

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Described mutations in Maine Coon cats

A study about HCM in Maine Coon cats was published (this is the first animal model in context of HCM). A31P mutation in exon 3 of MYBPC3 gene was found in all Maine Coon cats suffered from HCM and was not found in healthy Maine Coon cats even in 100 control samples (Meurs et. al. 2005). Computer analysis showed A31P mutation (G to C substitution in codon 31) modifies myosin binding protein C structure (reducing of alpha helix number and increasing non-specific convolution in protein structure). A74T polymorphism showed no correlation with HCM phenotype (Longerich et al.).

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Described mutations in ragdoll breed

In ragdoll breed a mutation in different MYBPC3 protein domain than in Maine Coon breed has been identified. This mutation is a C to T substitution, which causes amino acid arginine to tryptophan change at position 820 (R820W). This mutation was found in all HCM affected animals and was not found in animals without HCM even in control samples (Meurs et. al. 2007). It is assumed that the arginine to tryptophan (large aromatic amino acid) substitution causes changes in the protein secondary structure that prevent optimal myosin binding protein C conformation.

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Genetic testing of HCM

Genetic tests can be realized at any age of animal. Testing can be done from cheek swab sample (non-invasive sampling method, suitable for all non-breast-fed animals; cheek swabbing can be easily performed by each breeder) or blood sample.

There is no other HCM genetic test available for other cat breeds. There is a research focused on connection between genes and disease HCM in other cat breeds.

We recommend genetic testing for Maine Coon and ragdoll to prevent the transmission of mutations to offspring. Genetically positive HCM animals would not be put into breeding. For cats in a breeding program annual cardiology examination is recommended.

A notice for cat breeders: negative molecular genetic testing result or negative cardiology finding do not guarantee that a cat becomes ill with any other form of cardiomyopathy. Molecular genetic testing reveals the specific mutations A31P in Maine Coon cats and R820W in ragdoll cats only. It cannot be excluded there are other mutations causing HCM disease. Nowadays, there is no certain evidence of genotype impact to HCM phenotype. It is necessary to confront a genetic test result with clinical cardiological examination.

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References:

K.M. Meurs, et al.: A cardiac myosin binding protein C mutation in the Maine coon cat with familial hypertrophic cardiomyopathy, Hum. Mol. Genet. 14 (2005) 3587-3593.

K. M. Meurs, et al.: A substitution in the myosin binding protein C gene in ragdoll hypertrophic cardiomyopathy, Genomics 90 (2007) 261-264

Longeri M, Ferrari P, Knafelz P, Mezzelani A, Marabotti A, Milanesi L, Pertica G, Polli M, Brambilla PG, Kittleson M, Lyons LA, Porciello F.: Myosin-binding protein C DNA variants in domestic cats (A31P, A74T, R820W) and their association with hypertrophic cardiomyopathy. J Vet Intern Med. 2013 Mar-Apr;27(2):275-85.