A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy

Kathryn M. Meurs, Ximena Sanchez, Ryan M. David, Neil E. Bowles, Jeffrey A. Towbin, Peter J. Reiser, Judith A. Kittleson, Marcia J. Munro, Keith Dryburgh, Kristin A. MacDonald, Mark D Kittleson

Research output: Contribution to journalArticle

141 Citations (Scopus)

Abstract

Hypertrophic cardiomyopathy (HCM) is one of the most common causes of sudden cardiac death in young adults and is a familial disease in at least 60% of cases. Causative mutations have been identified in several sarcomeric genes, including the myosin binding protein C (MYBPC3) gene. Although numerous causative mutations have been identified, the pathogenetic process is still poorly understood. A large animal model of familial HCM in the cat has been identified and may be used for additional study. As the first spontaneous large animal model of this familial disease, feline familial HCM provides a valuable model for investigators to evaluate pathophysiologic processes and therapeutic (pharmacologic or genetic) manipulations. The MYBPC3 gene was chosen as a candidate gene in this model after identifying a reduction in the protein in myocardium from affected cats in comparison to control cats (P < 0.001). DNA sequencing was performed and sequence alterations were evaluated for evidence that they changed the amino acid produced, that the amino acid was conserved and that the protein structure was altered. We identified a single base pair change (G to C) in the feline MYBPC3 gene in affected cats that computationally alters the protein conformation of this gene and results in sarcomeric disorganization. We have identified a causative mutation in the feline MYBPC3 gene that results in the development of familial HCM. This is the first report of a spontaneous mutation causing HCM in a non-human species. It should provide a valuable model for evaluating pathophysiologic processes and therapeutic manipulations.

Original languageEnglish (US)
Pages (from-to)3587-3593
Number of pages7
JournalHuman Molecular Genetics
Volume14
Issue number23
DOIs
StatePublished - Dec 1 2005

Fingerprint

Familial Hypertrophic Cardiomyopathy
Cardiac Myosins
Cats
Mutation
Felidae
Genes
Hypertrophic Cardiomyopathy
Genetic Phenomena
Animal Disease Models
Amino Acids
Protein Conformation
Sudden Cardiac Death
myosin-binding protein C
DNA Sequence Analysis
Base Pairing
Young Adult
Myocardium
Proteins
Animal Models
Research Personnel

ASJC Scopus subject areas

  • Genetics

Cite this

A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy. / Meurs, Kathryn M.; Sanchez, Ximena; David, Ryan M.; Bowles, Neil E.; Towbin, Jeffrey A.; Reiser, Peter J.; Kittleson, Judith A.; Munro, Marcia J.; Dryburgh, Keith; MacDonald, Kristin A.; Kittleson, Mark D.

In: Human Molecular Genetics, Vol. 14, No. 23, 01.12.2005, p. 3587-3593.

Research output: Contribution to journalArticle

Meurs, KM, Sanchez, X, David, RM, Bowles, NE, Towbin, JA, Reiser, PJ, Kittleson, JA, Munro, MJ, Dryburgh, K, MacDonald, KA & Kittleson, MD 2005, 'A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy', Human Molecular Genetics, vol. 14, no. 23, pp. 3587-3593. https://doi.org/10.1093/hmg/ddi386
Meurs, Kathryn M. ; Sanchez, Ximena ; David, Ryan M. ; Bowles, Neil E. ; Towbin, Jeffrey A. ; Reiser, Peter J. ; Kittleson, Judith A. ; Munro, Marcia J. ; Dryburgh, Keith ; MacDonald, Kristin A. ; Kittleson, Mark D. / A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy. In: Human Molecular Genetics. 2005 ; Vol. 14, No. 23. pp. 3587-3593.
@article{5f6abf27d50947a2a21efb5db5ad4ab0,
title = "A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy",
abstract = "Hypertrophic cardiomyopathy (HCM) is one of the most common causes of sudden cardiac death in young adults and is a familial disease in at least 60{\%} of cases. Causative mutations have been identified in several sarcomeric genes, including the myosin binding protein C (MYBPC3) gene. Although numerous causative mutations have been identified, the pathogenetic process is still poorly understood. A large animal model of familial HCM in the cat has been identified and may be used for additional study. As the first spontaneous large animal model of this familial disease, feline familial HCM provides a valuable model for investigators to evaluate pathophysiologic processes and therapeutic (pharmacologic or genetic) manipulations. The MYBPC3 gene was chosen as a candidate gene in this model after identifying a reduction in the protein in myocardium from affected cats in comparison to control cats (P < 0.001). DNA sequencing was performed and sequence alterations were evaluated for evidence that they changed the amino acid produced, that the amino acid was conserved and that the protein structure was altered. We identified a single base pair change (G to C) in the feline MYBPC3 gene in affected cats that computationally alters the protein conformation of this gene and results in sarcomeric disorganization. We have identified a causative mutation in the feline MYBPC3 gene that results in the development of familial HCM. This is the first report of a spontaneous mutation causing HCM in a non-human species. It should provide a valuable model for evaluating pathophysiologic processes and therapeutic manipulations.",
author = "Meurs, {Kathryn M.} and Ximena Sanchez and David, {Ryan M.} and Bowles, {Neil E.} and Towbin, {Jeffrey A.} and Reiser, {Peter J.} and Kittleson, {Judith A.} and Munro, {Marcia J.} and Keith Dryburgh and MacDonald, {Kristin A.} and Kittleson, {Mark D}",
year = "2005",
month = "12",
day = "1",
doi = "10.1093/hmg/ddi386",
language = "English (US)",
volume = "14",
pages = "3587--3593",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "23",

}

TY - JOUR

T1 - A cardiac myosin binding protein C mutation in the Maine Coon cat with familial hypertrophic cardiomyopathy

AU - Meurs, Kathryn M.

AU - Sanchez, Ximena

AU - David, Ryan M.

AU - Bowles, Neil E.

AU - Towbin, Jeffrey A.

AU - Reiser, Peter J.

AU - Kittleson, Judith A.

AU - Munro, Marcia J.

AU - Dryburgh, Keith

AU - MacDonald, Kristin A.

AU - Kittleson, Mark D

PY - 2005/12/1

Y1 - 2005/12/1

N2 - Hypertrophic cardiomyopathy (HCM) is one of the most common causes of sudden cardiac death in young adults and is a familial disease in at least 60% of cases. Causative mutations have been identified in several sarcomeric genes, including the myosin binding protein C (MYBPC3) gene. Although numerous causative mutations have been identified, the pathogenetic process is still poorly understood. A large animal model of familial HCM in the cat has been identified and may be used for additional study. As the first spontaneous large animal model of this familial disease, feline familial HCM provides a valuable model for investigators to evaluate pathophysiologic processes and therapeutic (pharmacologic or genetic) manipulations. The MYBPC3 gene was chosen as a candidate gene in this model after identifying a reduction in the protein in myocardium from affected cats in comparison to control cats (P < 0.001). DNA sequencing was performed and sequence alterations were evaluated for evidence that they changed the amino acid produced, that the amino acid was conserved and that the protein structure was altered. We identified a single base pair change (G to C) in the feline MYBPC3 gene in affected cats that computationally alters the protein conformation of this gene and results in sarcomeric disorganization. We have identified a causative mutation in the feline MYBPC3 gene that results in the development of familial HCM. This is the first report of a spontaneous mutation causing HCM in a non-human species. It should provide a valuable model for evaluating pathophysiologic processes and therapeutic manipulations.

AB - Hypertrophic cardiomyopathy (HCM) is one of the most common causes of sudden cardiac death in young adults and is a familial disease in at least 60% of cases. Causative mutations have been identified in several sarcomeric genes, including the myosin binding protein C (MYBPC3) gene. Although numerous causative mutations have been identified, the pathogenetic process is still poorly understood. A large animal model of familial HCM in the cat has been identified and may be used for additional study. As the first spontaneous large animal model of this familial disease, feline familial HCM provides a valuable model for investigators to evaluate pathophysiologic processes and therapeutic (pharmacologic or genetic) manipulations. The MYBPC3 gene was chosen as a candidate gene in this model after identifying a reduction in the protein in myocardium from affected cats in comparison to control cats (P < 0.001). DNA sequencing was performed and sequence alterations were evaluated for evidence that they changed the amino acid produced, that the amino acid was conserved and that the protein structure was altered. We identified a single base pair change (G to C) in the feline MYBPC3 gene in affected cats that computationally alters the protein conformation of this gene and results in sarcomeric disorganization. We have identified a causative mutation in the feline MYBPC3 gene that results in the development of familial HCM. This is the first report of a spontaneous mutation causing HCM in a non-human species. It should provide a valuable model for evaluating pathophysiologic processes and therapeutic manipulations.

UR - http://www.scopus.com/inward/record.url?scp=28744456883&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=28744456883&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddi386

DO - 10.1093/hmg/ddi386

M3 - Article

C2 - 16236761

AN - SCOPUS:28744456883

VL - 14

SP - 3587

EP - 3593

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 23

ER -