Polysaccharide Storage Myopathy (PSSM 1)
Summary
Polysaccharide Storage Myopathy, type 1 (PSSM1) is associated with a semidominant variant of the GYS1 gene that encodes glycogen synthase (GYS1-R309H). The variant form of the enzyme is overactive, causing excess glycogen storage in muscle tissue. Many horses that carry this variant do not show symptoms. Horses affected with both PSSM1 (GYS1-R309H) and Malignant Hyperthermia (MH) (RYR1-R2454G) have higher exercise intolerance than those with PSSM1 alone.
Over 10% of Quarter Horses are affected. Over 60% of Percherons and 90% of Belgian Draft horses are affected. The American Quarter Horse Association requires genetic testing for PSSM1 and four other genetic conditions (GBED, HYPP, MH, and HERDA) when a Quarter Horse is registered.
A substantial fraction of horses that carry the GYS1-R309H variant are asymptomatic. There is some evidence that additional genetic factors modify the development of symptoms in horses carrying the GYS1-R309H variant. EquiSeq is currently searching for variants that affect the development of symptoms in horses carrying the GYS1-R309H variant.
There are cases of PSSM that are not associated with the GYS1-R309H variant. These cases are referred to as PSSM Type 2. The genetic basis of PSSM2 is under investigation. There appear to be multiple subtypes of PSSM2 in different breeds.
In most cases, a definitive diagnosis of PSSM2 requires both a muscle biopsy and a negative DNA test for the GYS1-R309H variant that is associated with PSSM1. This will change as the genetic causes of PSSM2 are identified.
Date of Last Update: 09/06/2016
Results
Understanding the Results
Results of the genetic test for PSSM1 are presented as shown below.
| Polysaccharide Storage Myopathy Type 1 (PSSM1) | ||
|---|---|---|
| n/n | Clear | This horse tested negative for P1 and does not carry the GYS1-R309H mutation identified in Quarter Horses. The horse will not pass on the defect to its offspring. |
| n/P1 | Affected | Both the normal and mutant alleles are present. This horse is positive for the GYS1-R309H (P1) mutation and may develop symptoms of exercise intolerance. |
| P1/P1 | Affected | This horse carries two copies of the GYS1-R309H (P1) mutation and may develop symptoms of exercise intolerance. |
Some horses carrying the GYS1-R309H (P1) mutation never develop symptoms of exercise intolerance, regardless of their diet or exercise program. It is possible that the effect of the GYS1-R309H mutation is modified by other genetic variants.
Disease Name and Genes
PSSM1 is associated with a G to A substitution in the GYS1 gene that causes an Arginine (R) to Histidine (H) substitution at amino acid position 309 in Glycogen Synthase I (GYS1-R309H).
Inheritance
PSSM1 is associated with a semidominant allele of the GYS1 gene (GYS1-R309H) that has incomplete penetrance. The semidominant allele is commonly abbreviated as P1, with the recessive wild-type allele abbreviated as n.
A horse with one copy of the semidominant allele (n/P1) will potentially have symptoms. If this horse is bred to a normal horse (n/n), each foal has a 50% chance of having one copy of the semidominant allele (n/P1) and a 50% chance of having two copies of the normal allele (n/n).
If two horses, each with one copy of the semidominant allele (n/P1), are bred, each foal has a 25% chance of having two copies of the normal allele (n/n), a 50% chance of having one copy of the semidominant allele (n/P1), and a 25% chance of having two copies of the semidominant allele (P1/P1). Because horses with one copy (n/P1) or two copies (P1/P1) of the semidominant allele are affected, each foal will have a 75% chance of potentially being affected.
If a horse with two copies of the semidominant allele (P1/P1) is bred to a normal horse (n/n), all of the foals will have one copy of the semidominant allele (n/P1) and will potentially be affected.
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