DNA tests for Exertional Myopathy (EM)
Some symptoms of exertional myopathy can be explained by variants in specific genes involved in muscle cell integrity (MIM) or energy metabolism (PSSM), which can be identified through DNA testing. Important tests include the PSSM1 test and the MIM-6 Variant test (formerly known as the PSSM2 test)..
MIM-6-Var. Test (formerly PSSM2 test)
This covers genes associated with forms of exercise-induced myopathy in which the symptoms are primarily due to impaired muscle cell integrity. Such integrity issues arise, for example, when structural proteins cannot be formed correctly or when the muscle cell is damaged due to a failure to neutralise internal metabolic toxic waste.
MIM-6-Var. Test | also included in:
| Gene | Variant | Disease / Link | Effect |
|---|---|---|
| MYOT | P2 | MIM - MFM (Myotilinopathy) Link EquiSeq | Stability of muscle fibers during contraction |
| FLNC | P3 | MIM - MFM (Filaminopathye) Link EquiSeq | Integrity of the longitudinal connections (Z-disc) of muscle fibers |
| MYOZ3 | P4 | MIM - MFM (Myozeninopathy) Link EquiSeq | Anchoring of contractile proteins to the Z-disc |
| PYROXD1 | P8 | MIM - PYROXD1 Link EquiSeq | Involved in cellular detoxification and the neutralization of reactive oxygen species |
| COLA6A3 | K1 | MIM - COL6A3 Link EquiSeq | Involved in the endomysium, the internal supportive structure of muscle fibers |
| CACNA2D3 | Px | im MIM - CACNA2D3 Link EquiSeq | Indirect marker for variants affecting signal transmission involved in muscle contraction |
PSSM 1 Test
PSSM (Polysaccharide Storage Myopathy) Type 1 is caused by a defect in the enzyme GYS1 (glycogen synthase 1). The GYS1 mutation leads to upregulation of the produced enzyme. Increased glycogen synthesis results in an excess accumulation when the glycogen is not sufficiently utilized. The consequence is an abnormal storage of glycogen within the musculature, which subsequently leads to clinical symptoms.
The term PSSM2 originated from the observation that some symptomatic horses diagnosed with PSSM based on muscle biopsy findings did not carry a GYS1 mutation.
The gene variants now grouped under the term MIM-6 Variant Test (see above) — including P2, P3, P4, P8, and K1 — were initially proposed as candidate variants responsible for these PSSM2 cases and were marketed as such.
However, as expanded mutation screening indicated that these variants appear to exert their effects independently of glycogen metabolism, the new nomenclature using the umbrella term MIM (Muscle Integrity Myopathy) was introduced.
Consequently, there is currently no DNA test specifically for PSSM2 as a subgroup of PSSM. Confirmation or exclusion requires a muscle biopsy, although important limitations and considerations regarding this procedure must be taken into account.
DNA Test PSSM1 | also included in:
Malignant Hyperthermia
Malignant Hyperthermia (MH) is caused by a mutation in the RYR1 gene. The mutation is inherited in a dominant manner, meaning that a single defective gene copy is sufficient to trigger muscle breakdown associated with high fever and respiratory distress when certain anesthetic agents are administered or when affected horses are subjected to exertion. MH results in the death of the horse in approximately 34% of cases. The condition occurs primarily in Quarter Horses and related breeds but has become very rare due to the availability of genetic testing.
DNA Test MH | also included in:
MYH1-Myopathy (formerly IMM)
MYH1 myopathy is an autoimmune disorder in which a horse develops an immune reaction against certain of its own muscle proteins. Two clinical forms of MYHM are recognized:
- immune-mediated myopathy (IMM), and
- non-exertional rhabdomyolysis.
The tested gene mutation represents a risk factor for these conditions. The disease shows incomplete autosomal dominant inheritance and occurs in Quarter Horses and related breeds.
DNA Test MYH1 | also included in: