• 1. Meurs KM, Fox PR, Norgard M, et al. A prospective genetic evaluation of familial dilated cardiomyopathy in the Doberman Pinscher. J Vet Intern Med 2007;21:10161020.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. Meurs KM, Lahmers S, Keene BW, et al. A splice site mutation in a gene encoding for PDK4, a mitochondrial protein, is associated with the development of dilated cardiomyopathy in the Doberman Pinscher. Hum Genet 2012;131:13191325.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. Meurs KM, Friedenberg SG, Kolb J, et al. A missense variant in the titin gene in Doberman Pinscher dogs with familial dilated cardiomyopathy and sudden cardiac death. Hum Genet 2019;138:515524.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4. Mausberg TB, Wess G, Simak J, et al. A locus on chromosome 5 is associated with dilated cardiomyopathy in Doberman Pinschers. PLoS One 2011;6:e20042.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5. Paldino A, De Angelis G, Merlo M, et al. Genetics of dilated cardiomyopathy: clinical implications. Curr Cardiol Rep 2018;20:83.

  • 6. Wilcox JE, Hershberger RE. Genetic cardiomyopathies. Curr Opin Cardiol 2018;33:354362.

  • 7. Belanger MC. Echocardiography. In: Ettinger SJ, Feldman EC, Cote E, eds. Textbook of veterinary internal medicine. 8th ed. St Louis: Elsevier, 2017;393410.

    • Search Google Scholar
    • Export Citation
  • 8. Wess G, Schulze A, Butz V, et al. Prevalence of dilated cardiomyopathy in Doberman Pinschers in various age groups. J Vet Intern Med 2010;24:533538.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9. Reichart D, Magnussen C, Zeller T, et al. Dilated cardiomyopathy: from epidemiologic to genetic phenotypes: a translational review of current literature. J Intern Med 2019;286:362372.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Zhang Y, Maccosham A. Mind the gap: genetic variation and personalized therapies for cardiomyopathies. Lifestyle Genom 2018;11:7779.

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Assessment of PDK4 and TTN gene variants in 48 Doberman Pinschers with dilated cardiomyopathy

Kathryn M. Meurs1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Joshua A. Stern2Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA 95616.

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Darcy Adin1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Bruce W. Keene1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Theresa C. De Francesco1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Sandra P. Tou1Department of Veterinary Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607.

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Abstract

OBJECTIVE

To evaluate the frequency of variants in the pyruvate kinase dehydrogenase 4 (PDK4) and titin (TTN) genes in a group of Doberman Pinschers with dilated cardiomyopathy (DCM) and to determine whether there were unique clinical attributes to each variant.

ANIMALS

48 Doberman Pinschers with DCM.

PROCEDURES

Doberman Pinschers with recently diagnosed DCM were identified, and genomic DNA from each was genotyped with a PCR assay for detection of PDK4 and TTN genetic variants. Dogs were grouped on the basis of whether they had the TTN variant alone, PDK4 variant alone, both variants, or neither variant. Descriptive statistics were compiled for dog age, body weight, and left ventricular dimensions and fractional shortening and for the presence of ventricular and supraventricular arrhythmias and heart failure. Results were compared across groups.

RESULTS

Of the 48 dogs, 28 had the TTN variant alone, 10 had both variants, 6 had neither variant, and 4 had the PDK4 variant alone. The mean age was younger for dogs with the PDK4 variant alone, compared with other dogs. However, the number of dogs with the PDK4 variant alone was very small, and there was an overlap in age across groups. No other meaningful differences were detected across groups, and independent genotype-phenotype relationships were not identified.

CONCLUSIONS AND CLINICAL RELEVANCE

Although findings indicated that the TTN variant was most common, 6 dogs had neither variant, and this fact supported the concept of ≥ 1 other genetic contributor to DCM in Doberman Pinschers. Future studies are warranted to evaluate genotype-phenotype relationships in Doberman Pinschers with DCM.

Abstract

OBJECTIVE

To evaluate the frequency of variants in the pyruvate kinase dehydrogenase 4 (PDK4) and titin (TTN) genes in a group of Doberman Pinschers with dilated cardiomyopathy (DCM) and to determine whether there were unique clinical attributes to each variant.

ANIMALS

48 Doberman Pinschers with DCM.

PROCEDURES

Doberman Pinschers with recently diagnosed DCM were identified, and genomic DNA from each was genotyped with a PCR assay for detection of PDK4 and TTN genetic variants. Dogs were grouped on the basis of whether they had the TTN variant alone, PDK4 variant alone, both variants, or neither variant. Descriptive statistics were compiled for dog age, body weight, and left ventricular dimensions and fractional shortening and for the presence of ventricular and supraventricular arrhythmias and heart failure. Results were compared across groups.

RESULTS

Of the 48 dogs, 28 had the TTN variant alone, 10 had both variants, 6 had neither variant, and 4 had the PDK4 variant alone. The mean age was younger for dogs with the PDK4 variant alone, compared with other dogs. However, the number of dogs with the PDK4 variant alone was very small, and there was an overlap in age across groups. No other meaningful differences were detected across groups, and independent genotype-phenotype relationships were not identified.

CONCLUSIONS AND CLINICAL RELEVANCE

Although findings indicated that the TTN variant was most common, 6 dogs had neither variant, and this fact supported the concept of ≥ 1 other genetic contributor to DCM in Doberman Pinschers. Future studies are warranted to evaluate genotype-phenotype relationships in Doberman Pinschers with DCM.

Contributor Notes

Dr. Adin's present address is the Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL 32608.

Address correspondence to Dr. Meurs (kate_meurs@ncsu.edu).