UC Davis School of Veterinary Medicine Veterinary Genetics Laboratory
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Hypertrophic Cardiomyopathy- HCM

Introduction

Hypertrophic Cardiomyopathy is the most common cardiac disease in cats. Affected cats are at risk of sudden cardiac death due to defects that produce increased left ventricular heart muscle thickness. In Ragdolls, the condition is inherited due to breed specific mutations in the cardiac myosin binding protein C gene (MYBPC3).

Procedure for collecting a feline DNA sample

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Ragdoll HCM

The breed-specific mutation for HCM in Ragdoll cats produces early onset of the disease with average age at diagnosis of 15 months. It also appears that homozygotes (2 copies) for the mutation have an earlier age of onset of disease than heterozygotes (1 copy). The mutation, known as R820W,  is a single base pair change in MYBPC3 that is thought to alter the shape and function of this essential protein for normal heart muscle development. The same R820W mutation has been recently found to be associated with HCM and left ventricular non-compaction in humans (see reference below, Ripoll et al. 2010).

The Veterinary Genetics Laboratory offers a test for the Ragdoll breed specific HCM mutation.

Results reported as:

Test Result Ragdoll HCM Status
N/N Normal, cat does not have the Ragdoll HCM mutation
N/HCMrd One copy of the Ragdoll HCM mutation present; cat is affected
HCMrd/HCMrd Two copies of the Ragdoll HCM mutation present; cat is affected

Note: This test only detects the mutation associated with HCM in Ragdoll cats and outcrosses as described by Meurs et al. 2007.

References:

Meurs K., X. Sanchez, R.M. David, N.E. Bowles, J.A. Towbin, P.J. Reiser, J.A. Kittleson, M.J. Munro, K. Dryburgh, K.A. MacDonald, M.D. Kittleson. A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy. Human Molecular Genetics (2005) Vol.14, No. 23, doi:10.1093/hmg/ddi386.

Meurs, K., M.M. Norgard, M.M. Ederer, K.P. Hendrix, M.D. Kittleson. A substitution mutation in the myosin binding protein C gene in ragdoll hypertrophic cardiomyopathy. Genomics 90 (2007) 261-264

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 JM, 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. 2010 Jun 12. [Epub ahead of print]

Abstract for reference R820W mutation in MYBPC3

Background: The R820W mutation in the MYBPC3 gene has been associated with the development of hypertrophic cardiomyopathy (HCM) in rag-doll cats, but had not been described in humans.

Aim: To describe the phenotype associated with the R820W mutation identified in a human family.

Methods: The R820W was identified by direct sequencing of the MYBPC3 gene in a 47 year old woman with HCM and left ventricular non-compaction (LVNC). Clinical and genetic studies of the R820W mutation were performed in her family.

Results: The index patient was homozygous for the mutation and had no additional mutations in the main sarcomeric genes (MYH7, TTNNT2, TNNI3, TPM1). She had HCM with LVNC and normal systolic function. One brother had died suddenly at age 43 years. Another brother diagnosed of LVNC with severe systolic dysfunction and a cardiac arrest was also homozygous for the mutation. One heterozygous 31 year old sister and three heterozygous sons of the index (ages 14, 20 and 23 years old) were clinically unaffected. The father of the index was apparently healthy and her mother had atrial fibrillation and an electrocardiographic diagnosis of left ventricular hypertrophy at age 86 years.

Conclusion: The R820W mutation in the MYBPC3 gene, previously associated with the HCM in rag-doll cats, causes both HCM and LVNC in homozygous human carriers, with mild or null clinical expression in heterozygous carriers.

Veterinary Genetics Laboratory, Tel 530-752-2211, Email VGL