An E321G MYH1 mutation is strongly associated with nonexertional rhabdomyolysis in Quarter Horses.
Abstract: An E321G mutation in MYH1 was recently identified in Quarter Horses (QH) with immune-mediated myositis (IMM) defined by a phenotype of gross muscle atrophy and myofiber lymphocytic infiltrates. Objective: We hypothesized that the MYH1 mutation also was associated with a phenotype of nonexertional rhabdomyolysis. The objective of this study was to determine the prevalence of the MYH1 mutation in QH with exertional (ER) and nonexertional (nonER) rhabdomyolysis. Methods: Quarter Horses: 72 healthy controls, 85 ER-no atrophy, 56 ER-atrophy, 167 nonER horses selected regardless of muscle atrophy. Methods: Clinical and histopathologic information and DNA was obtained from a database for (1) ER > 2 years of age, with or without atrophy and (2) nonER creatine kinase (CK) ≥ 5000 U/L, <5 years of age. Horses were genotyped for E321G MYH1 by pyrosequencing. Results: The MYH1 mutation was present in a similar proportion of ER-no atrophy (1/56; 2%) and in a higher proportion of ER-atrophy (25/85; 29%) versus controls (4/72; 5%). The MYH1 mutation was present in a significantly higher proportion of nonER (113/165; 68%) than controls either in the presence (39/42; 93%) or in absence (72/123; 59%) of gross atrophy. Lymphocytes were present in <18% of muscle samples with the MYH1 mutation. Conclusions: Although not associated with ER, the MYH1 mutation is associated with atrophy after ER. The MYH1 mutation is highly associated with nonER regardless of whether muscle atrophy or lymphocytic infiltrates are present. Genetic testing will enhance the ability to diagnose MYH1 myopathies (MYHM) in QH.
© 2018 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.
Publication Date: 2018-08-05 PubMed ID: 30079499PubMed Central: PMC6189380DOI: 10.1111/jvim.15299Google Scholar: Lookup
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Summary
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The research has discovered a strong relationship between a genetic mutation (E321G MYH1) and nonexertional rhabdomyolysis in Quarter Horses, this new found understanding could be used for diagnosis and treatment, potentially improving the health and welfare of these animals.
Introduction to the Study
- The research focuses on the E321G mutation in MYH1 that was previously recognized in Quarter Horses with immune-mediated myositis (muscle inflammation due to immune response). The experiment tests the hypothesis that this same mutation is also associated with nonexertional rhabdomyolysis, which is a breakdown of muscle unrelated to exercise.
- The aim of the research was to determine the occurrence of the E321G MYH1 mutation in horses with exertional rhabdomyolysis (muscle breakdown due to exercise) as well as non-exertional rhabdomyolysis.
Methodology
- The study utilized DNA from a variety of Quarter Horses: healthy controls, horses with exertional rhabdomyolysis but no atrophy (muscle loss), horses with exertional rhabdomyolysis and atrophy, and horses with nonexertional rhabdomyolysis, irrespective of atrophy.
- They looked specifically at horses with exertional rhabdomyolysis of over two years regardless of atrophy (muscle loss), and nonexertional rhabdomyolysis in horse of under five years with a certain level of creatine kinase, an enzyme that indicates muscle damage.
- All horses were genotyped for the E321G MYH1 mutation using a technique called pyrosequencing, which is an accurate and high-throughput method to identify genetic variation.
Results
- The E321G MYH1 mutation was found in similar portions of horses with exertional rhabdomyolysis but no atrophy (2%) and a higher portion of those with atrophy (29%) when compared to the control group (5%).
- The mutation was significantly more present in horses with nonexertional rhabdomyolysis (68%) regardless of atrophy or not, with or without lymphocytic infiltrates (presence of white blood cells).
- Only less than 18% of the muscle samples with the mutation showed presence of lymphocytes, indicating immune response.
Conclusion
- While the E321G MYH1 mutation wasn’t directly linked to exertional rhabdomyolysis, it was associated with muscle atrophy after exercise. The E321G MYH1 mutation is found to have a strong association with nonexertional rhabdomyolysis, whether or not muscle atrophy or lymphocytic infiltrates are present.
- The findings could enable genetic testing to be an effective tool in diagnosing MYH1-related myopathies (muscle disease) in Quarter Horses, thereby improving their health and welfare.
Cite This Article
APA
Valberg SJ, Henry ML, Perumbakkam S, Gardner KL, Finno CJ.
(2018).
An E321G MYH1 mutation is strongly associated with nonexertional rhabdomyolysis in Quarter Horses.
J Vet Intern Med, 32(5), 1718-1725.
https://doi.org/10.1111/jvim.15299 Publication
Researcher Affiliations
- McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan.
- McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan.
- McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan.
- McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Michigan.
- Department of Population Health and Reproduction, University of California-Davis, Davis, California.
MeSH Terms
- Animals
- Case-Control Studies
- DNA
- Female
- Genetic Predisposition to Disease
- Genotype
- Horse Diseases / genetics
- Horses
- Male
- Muscular Atrophy / veterinary
- Mutation
- Myosin Heavy Chains / genetics
- Rhabdomyolysis / genetics
- Rhabdomyolysis / veterinary
Grant Funding
- K01 OD015134 / NIH HHS
- L40 TR001136 / NCATS NIH HHS
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Citations
This article has been cited 7 times.- Durward-Akhurst SA, Valberg SJ. Myosin Heavy Chain Myopathy and Immune-Mediated Muscle Disorders. Vet Clin North Am Equine Pract 2025 Apr;41(1):61-75.
- Lopergolo D, Gallus GN, Pieraccini G, Boscaro F, Berti G, Serni G, Volpi N, Formichi P, Bianchi S, Cassandrini D, Sorrentino V, Rossi D, Santorelli FM, De Stefano N, Malandrini A. CCDC78: Unveiling the Function of a Novel Gene Associated with Hereditary Myopathy. Cells 2024 Sep 8;13(17).
- Valberg SJ, Schultz AE, Finno CJ, Bellone RR, Hughes SS. Prevalence of clinical signs and factors impacting expression of myosin heavy chain myopathy in Quarter Horse-related breeds with the MYH1(E321G) mutation. J Vet Intern Med 2022 May;36(3):1152-1159.
- Ochala J, Finno CJ, Valberg SJ. Myofibre Hyper-Contractility in Horses Expressing the Myosin Heavy Chain Myopathy Mutation, MYH1(E321G). Cells 2021 Dec 6;10(12).
- Raudsepp T, Finno CJ, Bellone RR, Petersen JL. Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post-genome era. Anim Genet 2019 Dec;50(6):569-597.
- Gianino GM, Valberg SJ, Perumbakkam S, Henry ML, Gardner K, Penedo C, Finno CJ. Prevalence of the E321G MYH1 variant for immune-mediated myositis and nonexertional rhabdomyolysis in performance subgroups of American Quarter Horses. J Vet Intern Med 2019 Mar;33(2):897-901.
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