Hypertrophic Cardiomyopathy (Maine Coon, Ragdoll types)

 

Gene: MYBPC3

Transmission: Autosomal dominant

The animal only has to have one copy of the mutation to be at risk of developing hypertrophic cardiomyopathy.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  Offspring are potentially at risk of developing the disease if at least one parent carries the mutation.

Mutations:

Maine Coon mutation: Substitution, MYBPC3 gene; c.91 G>C, p.(A31P), exon2

Ragdoll mutation: Substitution, MYBPC3 gene; c.2453 C>T, p.(R818W)

Medical system: Cardiac

Breeds: American Bobtail, Domestic Cat, Highland Lynx, Maine Coon, Munchkin, Pixie-bob, Ragamuffin, Ragdoll, Scottish Fold, Siberian

Age of onset of symptoms: By 4 years of age.

Hypertrophic cardiomyopathy is the most common heart disease in cats. In this disease the heart muscle is enlarged and left ventricular walls are thickened and are not dilated. Hypertrophic cardiomyopathy affects young cats as a genetic disease and older cats as a secondary disease to hyperthyroidism. At present, the causative mutations are known for the Maine Coon and Ragdoll breeds of cat. Homozygous animals, with two copies of the mutation in question, can develop a more severe hypertrophic cardiomyopathy.

Note that hypertrophic cardiomyopathy in the cat has complex genetics with a number of known gene mutations involved as well as unknown mutations yet to be identified.  Characterized mutations include:

MYBPC3 gene mutations, Maine Coon and Ragdoll.  OMIA link: [0515-9685]

ALMS1 gene mutation, Sphynx.  OMIA link: [2316-9685]
MYH7 gene mutation reported in a domestic shorthair cat.  OMIA link [22122-9685]

 

References:

Labgenvet blog

OMIA link: [0515-9685]

Boeykens F, Abitbol M, Anderson H, et al. (2024) Classification of feline hypertrophic cardiomyopathy-associated gene variants according to the American College of Medical Genetics and Genomics guidelines. Front Vet Sci 11:1327081.  [pm/38371598]

Akiyama N, Suzuki R, Saito T, et al. (2023) Presence of known feline ALMS1 and MYBPC3 variants in a diverse cohort of cats with hypertrophic cardiomyopathy in Japan. PLoS One 18:e0283433.  [pubmed/37071642]

Novo Matos J, Payne JR. (2023) Predicting development of hypertrophic cardiomyopathy and disease outcomes in cats. Vet Clin North Am Small Anim Pract 53(6) :1277-1292. [pubmed/37500329]

Stern JA, Rivas VN, Kaplan JL, et al. (2023) Hypertrophic cardiomyopathy in purpose-bred cats with the A31P mutation in cardiac myosin binding protein-C. Sci Rep 13:10319. [pubmed/37365215]

Anderson H, Davison S, Lytle KM, et al. (2022) Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats.  PLoS Genet. 16;18(6):e1009804.  [pubmed/35709088]

Kittleson MD, Côté E. (2021) The feline cardiomyopathies: 2. Hypertrophic cardiomyopathy. J Feline Med Surg 23:1028-1051, [pubmed/34693811]

Kittleson MD, Côté E. (2021) The feline cardiomyopathies: 1. General concepts. J Feline Med Surg 23:1009-1027. [pubmed/34693806]

O’Donnell K, Adi D, Atkins CE, et al. (2021) Absence of known feline MYH7 and MYBPC3 variants in a diverse cohort of cats with hypertrophic cardiomyopathy. Anim Genet 52:542-4. [pubmed/33970514]

Gil-Ortuño C, Sebastián-Marcos P, Sabater-Molina M, et al. (2020) Genetics of feline hypertrophic cardiomyopathy. Clin Genet 98:203-14. [pubmed/32215921]

McNamara JW, Schuckman M, Becker RC, Sadayappan S. (2020) A novel homozygous intronic variant in TNNT2 associates with feline cardiomyopathy. Front Physiol 11:608473. [pubmed/33304277]

Fox PR, Keene BW, Lamb K, Schober KE, et al. (2019) Long-term Incidence and Risk of Noncardiovascular and All-Cause Mortality in Apparently Healthy Cats and Cats With Preclinical Hypertrophic Cardiomyopathy. J Vet Intern Med 33(6):2572-86.  [pubmed/31605422]

Schober KE, Savino SI, Yildiz V. (2016)  Right Ventricular Involvement in Feline Hypertrophic Cardiomyopathy. J Vet Cardiol. 18(4):297-309. [pubmed/27667689]

Granström S, Godiksen MT, Christiansen M, et al. (2015) Genotype-phenotype correlation between the cardiac myosin binding protein C mutation A31P and hypertrophic cardiomyopathy in a cohort of Maine Coon cats: a longitudinal study. J Vet Cardiol. 17 Suppl 1:S268-81. [pubmed/26776585]

Kittleson MD, Meurs KM, Harris SP. (2015) The genetic basis of hypertrophic cardiomyopathy in cats and humans.  J Vet Cardio 17:S53-S73.  [pubmed/26776594]

Borgeat K, Casamian-Sorrosal D, Helps C, et al. (2014) Association of the myosin binding protein C3 mutation (MYBPC3 R820W) with cardiac death in a survey of 236 Ragdoll cats.  J Vet Cardiol 16(2) :73-80. [pubmed/24906243]

Wess G, Schinner C. et al. (2010) Association of A31P and A74T polymorphisms in the myosin binding protein C3 gene and hypertrophic cardiomyopathy in Maine Coon and other breed cats. J Vet Intern Med 24 :527-532. [pubmed/20412438]

Fries R, Heaney AM, Meurs KM. (2008) Prevalence of the myosin-binding protein C mutation in Maine Coon cats.  J Vet Intern Med 22:893-896. [pubmed/18498321]

Meurs KM, Norgard MM, et al. (2007) A substitution mutation in the myosin binding protein C gene in ragdoll hypertrophic cardiomyopathy.  Genomics 90(2) :261-64. [pubmed/17521870]

Meurs KM, Sanchez X, David RM, et al. (2005) A cardiac myosin binding protein C mutation in the Maine coon cat with familial hypertrophic cardiomyopathy.  Hum. Mol. Genet. 14:3587-93. [pubmed/16236761]