M.E. McCue; S.J. Valberg; M. Jackson; M. Lucio; J.R. Mickelson
Polysaccharide Storage Myopathy (PSSM) is a common cause of neuromuscular disease in Quarter Horse related breeds, Draft and Warmblood horses when diagnosed by the presence of abnormal, amylase-resistant polysaccharide in skeletal muscle specimens. Using less stringent diagnostic criteria of increased amylase-sensitive glycogen, PSSM has also been diagnosed in a variety of other light breeds. Recently, a genome wide association study was used to identify a dominant mutation in the GYS1 gene of Quarter Horses with PSSM. This GYS1 mutation was present in 80% of PSSM Quarter Horses that were evaluated in the genome wide association study. In 20% of PSSM Quarter Horses in that study, PSSM was not linked to the GYS1 gene, suggesting that there may be a separate, non-GYS1 (type 2) form of PSSM.
The first objective of this study was to determine the prevalence of the GYS1 mutation in PSSM horses (biopsy diagnosis) from diverse breeds. The second objective was to determine if the prevalence of the GYS1 mutation differed between horses diagnosed with PSSM based on grade 1 (amylase-sensitive) or grade 2 (amylase-resistant) polysaccharide. 901 PSSM horses from 36 different breeds, as well as horses of mixed breed origin were identified from the Neuromuscular Disease Laboratory database. 831 cases had whole blood or tissue that was available for DNA isolation and genotyping for the GYS1 mutation. Cases were genotyped using a restriction fragment polymorphism assay.
The PSSM mutation was identified in horses from 17 different breeds including Quarter Horses, Paints, Appaloosas, 5 Draft horse breeds, Haflingers, 3 Warmblood breeds, Morgans, Mustangs, Rocky Mountain Horses and Tennessee Walking Horses, as well as mixed breed horses. The prevalence of the GYS1 mutation in PSSM horses was high in Draft (87%) and Quarter Horse related breeds (72%) and lower in Warmbloods and other light horse breeds, based on grade 2 diagnostic criteria. Overall, the PSSM mutation was present in 16% of grade 1 and 70% of grade 2 PSSM cases.
In conclusion, the GYS1 mutation causes PSSM in at least 17 different horse breeds and is the predominant form of PSSM in Draft-related and Quarter Horse-related breeds. Muscle biopsies from horses with the GYS1 mutation are most often characterized by the presence of abnormal, amylase-resistant polysaccharide inclusions. False positive diagnosis, as well as the possibility of a second glycogenosis in horses with neuromuscular disease (type 2 PSSM), may explain the absence of the GYS1 mutation in horses diagnosed with excessive glycogen accumulation in muscle.