Polysaccharide storage myopathy phenotype in quarter horse-related breeds is modified by the presence of an RYR1 mutation.

The research studies a family of Quarter Horses to identify a possible gene modifier affecting the severity of Polysaccharide Storage Myopathy (PSSM), a muscular disease. The study found that a mutation in the RYR1 gene, associated with malignant hyperthermia, was common among the horses with a more severe PSSM condition, suggesting the RYR1 mutation may exacerbate PSSM symptoms.

Objective and Methodology

• The aim of this research was to identify a gene which could be moderating the severity of Polysaccharide Storage Myopathy (PSSM), an equine muscle disease in a particular family of Quarter Horses. The horses in the study already had a dominant mutation in the GYS1 gene, which is linked to PSSM. The study sought to discover why some horses presented more severe symptoms than others.
• Using a genetic association analysis method, researchers identified the ryanodine receptor 1 (RYR1) as a potential gene that could influence the severity of the PSSM. This gene is known to be associated with malignant hyperthermia (MH).

Findings

• A rare equine mutation of the RYR1 gene, one associated with malignant hyperthermia, was identified in the family of Quarter Horses with the GYS1 PSSM mutation. This suggests that the presence of the RYR1 mutation alongside the GYS1 mutation could be contributing to the differing severity of symptoms in PSSM affected horses.
• Analysis of patient records for 179 horses supported this suggestion: horses carrying both the RYR1 and GYS1 mutations exhibited a more severe spectrum of clinical problems than those with the GYS1 mutation alone.
• A treadmill trial, involving 8 horses, also supported this conclusion. During the trial, serum creatine kinase activity was found to be higher and exercise intolerance greater in horses carrying both mutations, compared to those carrying only the GYS1 mutation.

Conclusions and implications

• The study concluded that a mutation in the RYR1 gene could modify the Polysaccharide Storage Myopathy phenotype in horses, causing a more severe clinical representation of the disease.
• The findings could have significant implications for the effective diagnosis and treatment of PSSM. Recognizing the presence of an RYR1 mutation alongside a GYS1 mutation could help predict the severity of the disease in Quarter Horses and potentially could inform targeted treatments.