OMIA 000515-9685 : Cardiomyopathy, hypertrophic in Felis catus

In other species: woolly monkeys , dog , pig , Arabian camel , cattle , golden hamster

Possibly relevant human trait(s) and/or gene(s) (MIM number): 192600

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2005

Cross-species summary: Increase in volume of the muscle tissue of the heart, due to an increase in the size of muscle cells, primarily in the left ventricle and ventricular septum.

Species-specific name: Feline familial HCM

Species-specific symbol: HCM

Species-specific description: Feline hypertrophic cardiomyopathy (HCM), characterized by left ventricular hypertrophy, is the most common heart disease in domestic cats. Causative mutations in MYBPC3 have been identified in Maine Coon cats and Ragdolls. Affected cats can appear clinically normal, or they can present with signs of arterial thromboembolism or congestive heart failure. A test is available for Maine Coon and Ragdoll cats.

Edited by Meg Sleeper, VMD and Vicki N. Meyers-Wallen, VMD, PhD, Dipl. ACT

Inheritance: The mode of inheritance is autosomal dominant with 100% penetrance (Kittleson et al., 1999).

Molecular basis: HCM is genetically heterogeneous in the overall cat population. By sequencing a very likely comparative candidate gene (based on the homologous human disorder), Meurs et al. (2005) identified the causative mutation in Maine Coon cats as a G to C substitution in exon 3, codon 31 of MYBPC3. This changes a conserved amino acid (alanine to proline; A31P), which most likely changes protein conformation. The exact role of this myosin binding protein C, cardiac is still unknown, though it may bind myosin or actin, or interact with other cardiac proteins that form sarcomeres (Meurs et al., 2005). Affected Maine Coon cats were found to be either heterozygous or homozygous for the A31P mutation.

Meurs et al. (2007) identified the causative mutation in Ragdoll cats as a C to T substitution in the same gene (MYBPC3), which changes the amino acid from arginine to tryptophan (R820W). As a result, the secondary structure of the myosin binding protein is changed, affecting sarcomere function.

Wess et al. (2010) proposed that a third mutation A74T is causative in Maine Coons, but the explanations by Kittleson et al. (2010) and the extensive data of Longeri et al. (2013) have, in essence, disproved this claim.

Clinical features: Affected cats can appear clinically normal, but left ventricular hypertrophy can be identified by ultrasonography. First signs appear in young adults or adults, although Ragdoll cats may have an earlier onset than other breeds. Clinical presentation can include signs of arterial thromboembolism, such as bilaterally painful, contracted hindlimb muscles, bilateral hindlimb ischemia, and pulseless rear limbs with blanched pads. Other affected cats present with signs of congestive heart failure and associated pulmonary edema. Clinical severity may be correlated to genotype (heterozygous vs. homozygous for the causative mutation, Meurs et al., 2005).

Pathology: Cardiac hypertrophy occurs in the absence of increased pressure or metabolic stimuli. Histologically, the cardiac muscle shows myofibrillar or myocyte disarray (Kittleson et al., 1999). The MYBPC3 mutations do not eliminate the protein, but reduce the amount present in cardiac muscle.

Prevalence: Hypertrophic cardiomyopathy is the most common cardiac disease in domestic cats.

Longeri et al. (2013) reported the results of an extensive survey of the three reported mutations (see Molecular Basis section) in 1855 cats of 28 breeds, with echocardiograph data available of 446 of these cats: "The MYBPC3 A31P and R820W were restricted to MCO [Maine Coon] and RD Ragdoll] respectively. Both purebred and random bred cats had HCM and the incidence increased with age. The A74T polymorphism was not associated with any phenotype. HCM was most prevalent in MCO homozygote for the A31P mutation and the penetrance increased with age. The penetrance of the heterozygote genotype was lower (0.08) compared to the P/P genotype (0.58) in MCO. . . . A31P mutation occurs frequently in MCO cats. The high incidence of HCM in homozygotes for the mutation supports the causal nature of the A31P mutation. Penetrance is incomplete for heterozygotes at A31P locus, at least at a young age. The A74T variant does not appear to be correlated with HCM."

Control: A test is available for MYBPC3 mutations in Maine Coon and Ragdoll cats.

Breeding of affected cats is not recommended.

Genetic testing: Tests are available for the Maine Coon and Ragdoll breeds. However, clinically affected cats may not have the mutation identified in those breeds, suggesting other possible causes.

Breeds: Maine Coon, Ragdoll.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MYBPC3 myosin binding protein C, cardiac Felis catus - no genomic information (-..-) MYBPC3 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective.

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Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Maine Coon Cardiomyopathy, hypertrophic MYBPC3 missense c.91G>C p.A31P 2005 16236761
Ragdoll Cardiomyopathy, hypertrophic MYBPC3 missense c.??C>T p.R820W 2007 17521870

References


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2016 Li, R.H., Stern, J.A., Ho, V., Tablin, F., Harris, S.P. :
Platelet Activation and Clopidogrel Effects on ADP-Induced Platelet Activation in Cats with or without the A31P Mutation in MYBPC3. J Vet Intern Med 30:1619-1629, 2016. Pubmed reference: 27615120. DOI: 10.1111/jvim.14568.
Schober, K.E., Savino, S.I., Yildiz, V. :
Right ventricular involvement in feline hypertrophic cardiomyopathy. J Vet Cardiol :, 2016. Pubmed reference: 27667689. DOI: 10.1016/j.jvc.2016.08.001.
2015 Borgeat, K., Stern, J., Meurs, K.M., Fuentes, V.L., Connolly, D.J. :
The influence of clinical and genetic factors on left ventricular wall thickness in Ragdoll cats. J Vet Cardiol 17 Suppl 1:S258-67, 2015. Pubmed reference: 26776584. DOI: 10.1016/j.jvc.2015.06.005.
Christiansen, L.B., Prats, C., Hyttel, P., Koch, J. :
Ultrastructural myocardial changes in seven cats with spontaneous hypertrophic cardiomyopathy. J Vet Cardiol 17 Suppl 1:S220-32, 2015. Pubmed reference: 26776581. DOI: 10.1016/j.jvc.2015.10.003.
Granström, S., Godiksen, M.T., Christiansen, M., Pipper, C.B., Martinussen, T., Møgelvang, R., Søgaard, P., Willesen, J.L., Koch, J. :
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, 2015. Pubmed reference: 26776585. DOI: 10.1016/j.jvc.2015.10.005.
Häggström, J., Luis Fuentes, V., Wess, G. :
Screening for hypertrophic cardiomyopathy in cats. J Vet Cardiol 17 Suppl 1:S134-49, 2015. Pubmed reference: 26776573. DOI: 10.1016/j.jvc.2015.07.003.
Jackson, B.L., Adin, D.B., Lehmkuhl, L.B. :
Effect of atenolol on heart rate, arrhythmias, blood pressure, and dynamic left ventricular outflow tract obstruction in cats with subclinical hypertrophic cardiomyopathy. J Vet Cardiol 17 Suppl 1:S296-305, 2015. Pubmed reference: 26776587. DOI: 10.1016/j.jvc.2015.03.002.
Kittleson, M.D., Meurs, K.M., Harris, S.P. :
The genetic basis of hypertrophic cardiomyopathy in cats and humans. J Vet Cardiol 17 Suppl 1:S53-73, 2015. Pubmed reference: 26776594. DOI: 10.1016/j.jvc.2015.03.001.
Maron, B.J., Fox, P.R. :
Hypertrophic cardiomyopathy in man and cats. J Vet Cardiol 17 Suppl 1:S6-9, 2015. Pubmed reference: 26776595. DOI: 10.1016/j.jvc.2015.03.007.
Payne, J.R., Borgeat, K., Brodbelt, D.C., Connolly, D.J., Luis Fuentes, V. :
Risk factors associated with sudden death vs. congestive heart failure or arterial thromboembolism in cats with hypertrophic cardiomyopathy. J Vet Cardiol 17 Suppl 1:S318-28, 2015. Pubmed reference: 26776589. DOI: 10.1016/j.jvc.2015.09.008.
Payne, J.R., Brodbelt, D.C., Luis Fuentes, V. :
Cardiomyopathy prevalence in 780 apparently healthy cats in rehoming centres (the CatScan study). J Vet Cardiol 17 Suppl 1:S244-57, 2015. Pubmed reference: 26776583. DOI: 10.1016/j.jvc.2015.03.008.
Stanzani, G., Cowlam, R., English, K., Connolly, D.J. :
Evaluation of red blood cell distribution width in cats with hypertrophic cardiomyopathy. J Vet Cardiol 17 Suppl 1:S233-43, 2015. Pubmed reference: 26776582. DOI: 10.1016/j.jvc.2015.09.001.
2014 Casamian-Sorrosal, D., Chong, S.K., Fonfara, S., Helps, C. :
Prevalence and demographics of the MYBPC3-mutations in ragdolls and Maine coons in the British Isles. J Small Anim Pract 55:269-73, 2014. Pubmed reference: 24602043. DOI: 10.1111/jsap.12201.
2013 Longeri, M., Ferrari, P., Knafelz, P., Mezzelani, A., Marabotti, A., Milanesi, L., Pertica, G., Polli, M., Brambilla, P.G., Kittleson, M., Lyons, L.A., Porciello, F. :
Myosin-binding protein C DNA variants in domestic cats (A31P, A74T, R820W) and their association with hypertrophic cardiomyopathy. J Vet Intern Med 27:275-85, 2013. Pubmed reference: 23323744. DOI: 10.1111/jvim.12031.
2012 Kershaw, O., Heblinski, N., Lotz, F., Dirsch, O., Gruber, A.D. :
Diagnostic value of morphometry in feline hypertrophic cardiomyopathy. J Comp Pathol 147:73-83, 2012. Pubmed reference: 22297077. DOI: 10.1016/j.jcpa.2011.11.196.
2011 Godiksen, M.T., Granstrøm, S., Koch, J., Christiansen, M. :
Hypertrophic cardiomyopathy in young Maine Coon cats caused by the p.A31P cMyBP-C mutation--the clinical significance of having the mutation. Acta Vet Scand 53:7, 2011. Pubmed reference: 21306647. DOI: 10.1186/1751-0147-53-7.
Swanson, W.F., Bateman, H.L., Newsom, J., Conforti, V.A., Herrick, J.R., Lambo, C.A., Haskins, M.E., Lyons, L.A., Kittleson, M.D., Harris, S.P., Fyfe, J.C., Magarey, G.M. :
Propagation of multiple cat hereditary disease models following assisted reproduction with frozen semen and embryos Reproduction, Fertility and Development 24:139-140 (Abstract 55), 2011.
2010 Abbott, JA. :
Feline hypertrophic cardiomyopathy: an update. Vet Clin North Am Small Anim Pract 40:685-700, 2010. Pubmed reference: 20610019. DOI: 10.1016/j.cvsm.2010.04.004.
Glaus, T., Wess, G. :
[Left ventricular hypertrophy in the cat - "when hypertrophic cardiomyopathy is not hypertrophic cardiomyopathy"]. Schweiz Arch Tierheilkd 152:325-30, 2010. Pubmed reference: 20582898. DOI: 10.1024/0036-7281/a000075.
Kittleson, MD., Meurs, K., Munro, M. :
Re: 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 24:1242-3; author reply 1244, 2010. Pubmed reference: 21054533. DOI: 10.1111/j.1939-1676.2010.0614.x.
Mary, J., Chetboul, V., Sampedrano, CC., Abitbol, M., Gouni, V., Trehiou-Sechi, E., Tissier, R., Queney, G., Pouchelon, JL., Thomas, A. :
Prevalence of the MYBPC3-A31P mutation in a large European feline population and association with hypertrophic cardiomyopathy in the Maine Coon breed. J Vet Cardiol 12:155-61, 2010. Pubmed reference: 21051304. DOI: 10.1016/j.jvc.2010.06.004.
Payne, J., Luis Fuentes, V., Boswood, A., Connolly, D., Koffas, H., Brodbelt, D. :
Population characteristics and survival in 127 referred cats with hypertrophic cardiomyopathy (1997 to 2005). J Small Anim Pract 51:540-7, 2010. Pubmed reference: 21029098. DOI: 10.1111/j.1748-5827.2010.00989.x.
Ripoll Vera, T., Monserrat Iglesias, L., Hermida Prieto, M., Ortiz, M., Rodriguez Garcia, I., Govea Callizo, N., Gómez Navarro, C., Rosell Andreo, J., Gámez Martínez, J.M., Pons Lladó, G., Cremer Luengos, D., Torres Marqués, J. :
The R820W mutation in the MYBPC3 gene, associated with hypertrophic cardiomyopathy in cats, causes hypertrophic cardiomyopathy and left ventricular non-compaction in humans. Int J Cardiol 145:405-7, 2010. Pubmed reference: 20542340. DOI: 10.1016/j.ijcard.2010.04.032.
Singh, MK., Cocchiaro, MF., Kittleson, MD. :
NT-proBNP measurement fails to reliably identify subclinical hypertrophic cardiomyopathy in Maine Coon cats. J Feline Med Surg 12:942-7, 2010. Pubmed reference: 21036088. DOI: 10.1016/j.jfms.2010.08.004.
Wess, G., Schinner, C., Weber, K., Küchenhoff, H., Hartmann, K. :
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 24:527-32, 2010. Pubmed reference: 20412438. DOI: 10.1111/j.1939-1676.2010.0514.x.
2009 Brizard, D., Amberger, C., Hartnack, S., Doherr, M., Lombard, C. :
Phenotypes and echocardiographic characteristics of a European population of domestic shorthair cats with idiopathic hypertrophic cardiomyopathy. Schweiz Arch Tierheilkd 151:529-38, 2009. Pubmed reference: 19885798. DOI: 10.1024/0036-7281.151.11.529.
Carlos Sampedrano, C., Chetboul, V., Mary, J., Tissier, R., Abitbol, M., Serres, F., Gouni, V., Thomas, A., Pouchelon, JL. :
Prospective echocardiographic and tissue Doppler imaging screening of a population of Maine Coon cats tested for the A31P mutation in the myosin-binding protein C gene: a specific analysis of the heterozygous status. J Vet Intern Med 23:91-9, 2009. Pubmed reference: 19175727. DOI: 10.1111/j.1939-1676.2008.0218.x.
Hsu, A., Kittleson, MD., Paling, A. :
Investigation into the use of plasma NT-proBNP concentration to screen for feline hypertrophic cardiomyopathy. J Vet Cardiol 11 Suppl 1:S63-70, 2009. Pubmed reference: 19395334. DOI: 10.1016/j.jvc.2009.02.005.
Meurs, KM., Norgard, MM., Kuan, M., Haggstrom, J., Kittleson, M. :
Analysis of 8 sarcomeric candidate genes for feline hypertrophic cardiomyopathy mutations in cats with hypertrophic cardiomyopathy. J Vet Intern Med 23:840-3, 2009. Pubmed reference: 19566849. DOI: 10.1111/j.1939-1676.2009.0341.x.
2008 Fries, R., Heaney, AM., Meurs, KM. :
Prevalence of the myosin-binding protein C mutation in Maine Coon cats. J Vet Intern Med 22:893-6, 2008. Pubmed reference: 18498321. DOI: 10.1111/j.1939-1676.2008.0113.x.
Gouni, V., Chetboul, V., Pouchelon, JL., Carlos Sampedrano, C., Maurey, C., Lefebvre, HP. :
Azotemia in cats with feline hypertrophic cardiomyopathy: prevalence and relationships with echocardiographic variables. J Vet Cardiol 10:117-23, 2008. Pubmed reference: 19027388. DOI: 10.1016/j.jvc.2008.09.002.
Jandrey, KE., Norris, JW., Macdonald, KA., Kittleson, MD., Tablin, F. :
Platelet function in clinically healthy cats and cats with hypertrophic cardiomyopathy: analysis using the Platelet Function Analyzer-100. Vet Clin Pathol 37:385-8, 2008. Pubmed reference: 19055572. DOI: 10.1111/j.1939-165X.2008.00062.x.
2007 Macdonald, KA., Kittleson, MD., Kass, PH., Meurs, KM. :
Tissue Doppler imaging in Maine Coon cats with a mutation of myosin binding protein C with or without hypertrophy. J Vet Intern Med 21:232-7, 2007. Pubmed reference: 17427382.
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 90:261-4, 2007. Pubmed reference: 17521870. DOI: 10.1016/j.ygeno.2007.04.007.
Riesen, SC., Kovacevic, A., Lombard, CW., Amberger, C. :
Echocardiographic screening of purebred cats: an overview from 2002 to 2005. Schweiz Arch Tierheilkd 149:73-6, 2007. Pubmed reference: 17343133.
2006 Kaneshige, T., Machida, N., Itoh, H., Yamane, Y. :
The anatomical basis of complete atrioventricular block in cats with hypertrophic cardiomyopathy. J Comp Pathol 135:25-31, 2006. Pubmed reference: 16844442. DOI: 10.1016/j.jcpa.2006.03.001.
Koffas, H., Dukes-McEwan, J., Corcoran, BM., Moran, CM., French, A., Sboros, V., Simpson, K., McDicken, WN. :
Pulsed tissue Doppler imaging in normal cats and cats with hypertrophic cardiomyopathy. J Vet Intern Med 20:65-77, 2006. Pubmed reference: 16496925.
Macdonald, KA., Kittleson, MD., Larson, RF., Kass, P., Klose, T., Wisner, ER. :
The effect of ramipril on left ventricular mass, myocardial fibrosis, diastolic function, and plasma neurohormones in Maine Coon cats with familial hypertrophic cardiomyopathy without heart failure. J Vet Intern Med 20:1093-105, 2006. Pubmed reference: 17063701.
2005 Cesta, MF., Baty, CJ., Keene, BW., Smoak, IW., Malarkey, DE. :
Pathology of end-stage remodeling in a family of cats with hypertrophic cardiomyopathy. Vet Pathol 42:458-67, 2005. Pubmed reference: 16006605. DOI: 10.1354/vp.42-4-458.
Macdonald, KA., Wisner, ER., Larson, RF., Klose, T., Kass, PH., Kittleson, MD. :
Comparison of myocardial contrast enhancement via cardiac magnetic resonance imaging in healthy cats and cats with hypertrophic cardiomyopathy. Am J Vet Res 66:1891-4, 2005. Pubmed reference: 16334945.
Meurs, KM., Sanchez, X., David, RM., Bowles, NE., Towbin, JA., Reiser, PJ., Kittleson, JA., Munro, MJ., Dryburgh, K., Macdonald, KA., Kittleson, MD. :
A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy. Hum Mol Genet 14:3587-93, 2005. Pubmed reference: 16236761. DOI: 10.1093/hmg/ddi386.
2004 Baty, CJ. :
Feline hypertrophic cardiomyopathy: an update. Vet Clin North Am Small Anim Pract 34:1227-34, 2004. Pubmed reference: 15325479. DOI: 10.1016/j.cvsm.2004.06.005.
2003 Connolly, D.J., Cannata, J., Boswood, A., Archer, J., Groves, E.A., Neiger, R. :
Cardiac troponin I in cats with hypertrophic cardiomyopathy Journal of Feline Medicine & Surgery 5:209-16, 2003.
Ferasin, L., Sturgess, CP., Cannon, MJ., Caney, SM., Gruffydd-Jones, TJ., Wotton, PR. :
Feline idiopathic cardiomyopathy: a retrospective study of 106 cats (1994-2001). J Feline Med Surg 5:151-9, 2003. Pubmed reference: 12765625.
Haggstrom, J. :
Hypertrophic cardiomyopathy in cats--it used to be so simple! J Feline Med Surg 5:139-41, 2003. Pubmed reference: 12670441.
2002 Herndon, W.E., Kittleson, M.D., Sanderson, K., Drobatz, K.J., Clifford, C.A., Gelzer, A., Summerfield, N.J., Linde, A., Sleeper, M.M. :
Cardiac troponin I in feline hypertrophic cardiomyopathy Journal of Veterinary Internal Medicine 16:558-564, 2002. Pubmed reference: 12322706.
Nakagawa, K., Takemura, N., Machida, N., Kawamura, M., Amasaki, H., Hirose, H. :
Hypertrophic cardiomyopathy in a mixed breed cat family. J Vet Med Sci 64:619-21, 2002. Pubmed reference: 12185318.
Rodriguez, D.B., Harpster, N. :
Feline hypertrophic cardiomyopathy: Etiology, pathophysiology, and clinical features Compendium on Continuing Education for the Practicing Veterinarian 24:364-+, 2002.
Rush, J.E., Freeman, L.M., Fenollosa, N.K., Brown, D.J. :
Population and survival characteristics of cats with hypertrophic cardiomyopathy: 260 cases (1990-1999) Journal of the American Veterinary Medical Association 220:202-207, 2002. Pubmed reference: 12126131.
2001 Baty, C.J., Malarkey, D.E., Atkins, C.E., DeFrancesco, T.C., Sidley, J., Keene, B.W. :
Natural history of hypertrophic cardiomyopathy and aortic thromboembolism in a family of domestic shorthair cats Journal of Veterinary Internal Medicine 15:595-599, 2001. Pubmed reference: 11817067.
Taugner, F.M. :
Stimulation of the renin-angiotensin system in cats with hypertrophic cardiomyopathy Journal of Comparative Pathology 125:122-129, 2001. Pubmed reference: 11578127. DOI: 10.1053/jcpa.2001.0486.
2000 Hayman, R., Une, Y., Nomura, Y. :
Desmin as a possible immunohistochemical marker for feline hypertrophic cardiomyopathy Journal of Veterinary Medical Science 62:343-346, 2000. Pubmed reference: 10770612.
Meurs, KM., Fox, PR., Magnon, AL., Liu, S., Towbin, JA. :
Molecular screening by polymerase chain reaction detects panleukopenia virus DNA in formalin-fixed hearts from cats with idiopathic cardiomyopathy and myocarditis. Cardiovasc Pathol 9:119-26, 2000. Pubmed reference: 10867362.
1999 Amberger, C.N., Glardon, O., Glaus, T., Hörauf, A., King, J.N., Schmidli, H., Schröter, L., Lombard, C.W. :
Effects of benazepril in the treatment of feline hypertrophic cardiomyopathy Results of a prospective, open-label, multicenter clinical trial. J Vet Cardiol 1:19-26, 1999. Pubmed reference: 19081318. DOI: 10.1016/S1760-2734(06)70026-1.
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1998 Baty, C., Watkins, H. :
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1997 Behrend, E.N., Grauer, G.F., Greco, D.S. :
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1996 Behrend, E.N., Grauer, G.F., Greco, D.S. :
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1995 Fox, P.R., Liu, S.K., Maron, B.J. :
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1993 Liu, S.K., Roberts, W.C., Maron, B.J. :
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1992 Atkins, CE., Gallo, AM., Kurzman, ID., Cowen, P. :
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1989 French, W. :
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1981 Liu, SK., Maron, BJ., Tilley, LP. :
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1977 Tilley, LP., Liu, SK., Gilbertson, SR., Wagner, BM., Lord, PF. :
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1975 Liu, SK., Tilley, LP., Lord, PF. :
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  • Created by Frank Nicholas on 22 Mar 2011
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  • Changed by Martha MaloneyHuss on 06 Sep 2011
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  • Changed by Frank Nicholas on 26 Nov 2012
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