Glycogen synthase 1 (GYS1) mutation in diverse breeds with polysaccharide storage myopathy.
Authors: McCue M E, Valberg S J, Lucio M, Mickelson J R
Journal: Journal of veterinary internal medicine
Summary
# GYS1 Mutation in Equine Polysaccharide Storage Myopathy: Prevalence and Breed Variation Polysaccharide storage myopathy (PSSM) affects horses across multiple disciplines, but the genetic basis has remained incompletely understood until recent years. McCue and colleagues screened 831 horses with histologically confirmed PSSM from 36 different breeds for a missense mutation in the GYS1 gene, using restriction fragment length polymorphism analysis to determine carrier status and correlate findings with the two recognised diagnostic grades of the disease. The GYS1 mutation proved highly prevalent in Draft breeds (87%) and Quarter Horse-related breeds (72%), but substantially lower in Warmbloods (18%) and other light horses (24%), with a striking overall difference between grade 1 PSSM horses (16% carrying the mutation) and grade 2 cases (70% carrying it). These findings demonstrate that GYS1 is the primary genetic cause of PSSM in certain breeds whilst highlighting that grade 1 PSSM—typically responsive to amylase treatment—likely represents either a distinct glycogenosis or diagnostic false-positives, warranting careful re-evaluation of horses negative for GYS1 despite clinical and histological signs. For practitioners, genetic testing of GYS1 is now a justified first-line screening tool in Draft and Quarter Horse breeds presenting with exertional myopathy, whilst recognition of breed-specific prevalence rates and the distinction between grades should inform both diagnosis and the expected utility of genetic testing across different equine populations.
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Practical Takeaways
- •Genetic testing for GYS1 mutation should be prioritized in Draft and Quarter Horse breeds with PSSM diagnosis, given 70-87% prevalence rates
- •Grade 2 polysaccharide accumulation on muscle biopsy strongly correlates with GYS1 mutation presence and should guide testing strategy
- •GYS1-negative PSSM cases may represent a distinct type 2 glycogenosis requiring different management approaches; consider alternative diagnoses or referral for further investigation
Key Findings
- •GYS1 mutation identified in horses from 17 different breeds with PSSM
- •High prevalence of GYS1 mutation in Draft breeds (87%) and Quarter Horse-related breeds (72%), compared to Warmbloods (18%) and other light horse breeds (24%)
- •GYS1 mutation present in 70% of grade 2 PSSM cases versus only 16% of grade 1 cases
- •GYS1 mutation is the predominant genetic cause of PSSM in Draft and Quarter Horse breeds, with a second glycogenosis (type 2 PSSM) potentially explaining GYS1-negative cases