Discovered at UC Davis Immune-Mediated Myositis (IMM/MYH1)

Quick Summary

Immune-mediated myositis (IMM) is an autoimmune muscle disease that can result in severe atrophy and extreme muscle loss. The genetic susceptibility to this condition is found in quarter horses and quarter horse-related breeds.
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Phenotype: Immune-mediated myositis (IMM) is characterized by infiltration of inflammatory cells from the immune system, particularly lymphocytes, into muscle fibers and surrounding blood vessels, with preferential targeting of the gluteal (rump) and epaxial (along the vertebral column) muscles. Signs include stiffness, weakness, and nonspecific malaise. Affected horses are usually 8 years and younger or 17 years and older, with no sex predilection.

Mode of Inheritance: Autosomal dominant (variable penetrance)

Alleles: N = Normal/Unaffected, My = MYH1 myopathy

Breeds appropriate for testing: Quarter Horse and related breeds

Explanation of Results:

  • Horses with N/N genotype will not have increased susceptibility for IMM or nonexertional rhabdomyolysis and cannot transmit this MYH1 myopathy variant to their offspring.
  • Horses with N/My genotype may develop IMM following infection or vaccination or nonexertional rhabdomyolysis. They may transmit this MYH1 myopathy variant to 50% of their offspring. Matings with N/N genotype will result in a 50% chance of producing a foal that may develop IMM.
  • Horses with My/My genotype are at risk and may develop IMM following infection or vaccination or nonexertional rhabdomyolysis. They will transmit this MYH1 myopathy variant to all of their offspring.
Price

$40 one test per animal

Panels Available
Additional Details

Quarter Horse and related breeds are susceptible to developing rapid onset of muscle atrophy and severe muscle damage at rest (nonexertional rhabdomyolysis). An autoimmune muscle disease called immune-mediated myositis (IMM) can cause this severe atrophy, which can result in the loss of 40% of muscle mass within 72 hours in Quarter Horse and related breeds.

IMM is characterized by infiltration of inflammatory cells, particularly lymphocytes, into muscle fibers and surrounding blood vessels, with preferential targeting of the gluteal (rump) and epaxial (along the vertebral column) muscles. IMM is characterized by stiffness, weakness, and nonspecific malaise. Affected horses are usually 8 years and younger or 17 years and older, with no sex predilection. Environmental factors combined with genetic susceptibility are important triggers for the development of muscle atrophy or severe rhabdomyolysis. About 39% of IMM horses have a history of exposure to a triggering factor such as Streptococcus equi subsp. equi infection, respiratory virus, or vaccination with influenza, Equine Herpes Virus 4, or Streptococcus equi subsp. equi.

Researchers at Michigan State University and University of California, Davis identified a mutation in the Myosin Heavy Chain 1 (MYH1) gene (Chr11:52,993,878T>C) that causes an amino acid change (denoted as p.E321G) detrimental to normal function of the myosin protein in muscle cells. In other words, a missense mutation in the DNA causes a change from a glutamic acid (E) to glycine (G) at position 321 of the protein.

This mutation is associated with increased susceptibility to develop IMM in Quarter Horses and related breeds characterized by significant muscle atrophy. Another clinical presentation of the MYH1 mutation in young Quarter Horses is severe, sudden muscle damage not associated with exercise (nonexertional rhabdomyolysis). Horses with nonexertional rhabdomyolysis do not necessarily have muscle atrophy.

IMM and nonexertional rhabdomyolysis belong to the group of muscle diseases known as MYH1 myopathy (MYHM). The mode of inheritance for MYHM is autosomal dominant with variable penetrance, which means that both males and females are affected and not all horses that have 1 (N/My) or 2 copies (My/My) of the mutation will develop IMM or nonexertional rhabdomyolysis. Horses with two copies (My/My) may be more severely affected. The frequency of the MYH1 mutation in the general Quarter Horse population is estimated at about 4%. About 7.5% of Quarter Horses have 1 copy of the mutation. The mutation frequency is higher in the reining (13.5%), working cow (8.5%) and halter (8%) categories, and not observed in barrel and racing categories.

Testing for IMM/MYHM can benefit clinicians by assisting with the diagnosis of IMM or nonexertional rhabdomyolysis cases suspected to be MYHM. The test assists breeders wanting to identify breeding stock that have 1 or 2 copies of the mutation in order to design appropriate breeding strategies that avoid producing at-risk offspring and help reduce the incidence of the disease in the breed.

Testing is recommended for Quarter Horses, Quarter Horse crosses, and related breeds with Quarter Horse influence.

Turnaround Time
2-6 business days
Type of Sample

Species

Type of Test

Results Reported As
Test Result Immune-Mediated Myositis (IMM/MYH1)
N/N No copies of the MYHM mutation. Horse does no have increased susceptibility for IMM or nonexertional rhabdomyolysis.
N/My 1 copy of the MYHM mutation is present. Horse may develop IMM following infection or vaccination, or nonexertional rhabdomyolysis. Horse can pass on the mutation to 50% of offspring.
My/My 2 copies of the MYHM mutation are present. Horse is at risk and may develop IMM following infection or vaccination, or nonexertional rhabdomyolysis. Horses will pass on the mutation to all offspring.
References

Lewis, S. S., Valberg, S. J., & Nielsen, I. L. (2007). Suspected immune-mediated myositis in horses. Journal of Veterinary Internal Medicine, 21(3), 495-503. doi: 10.1111/j.1939-1676.2007.tb02996.x

Durward-Akhurst, S. A., & Valberg, S. J. (2018). Immune-Mediated Muscle Diseases of the Horse. Veterinary Pathology, 55(1), 68-75. doi: 10.1177/0300985816688755

Finno, C. J., Gianino, G., Perumbakkam, S., Williams, Z. J., Bordbari, M. H., Gardner, K. L., Burns, E., Peng, S., Durward-Akhurst, S. A., & Valberg, S. J. (2018). A missense mutation in MYH1 is associated with susceptibility to Immune-mediated myositis in Quarter Horses. Skeletal Muscle, 8(1). doi: 10.1186/s13395-018-0155-0

Valberg, S.J., Henry, M.L., Perumbakkam, S., Gardner, K.L., & Finno, C.J. (2018). An E321G MYH1 mutation is strongly associated with nonexertional rhabdomyolysis in Quarter Horses. Journal of Veterinary Internal Medicine, 32(5), 1718-1725. doi: 10.1111/jvim.15299

Gianino, G.M., Valberg, S.J., Perumbakkam, S., Henry, M.L., Gardner, K., Penedo, C., & Finno, C.J. (2019). Prevalence of the E321G MYH1 variant for immune-mediated myositis and nonexertional rhabdomyolysis in performance subgroups of American Quarter Horses. Journal of Veterinary Internal Medicine, 33(2), 897-901. doi: 10.1111/jvim.15393