title: Polysaccharide storage myopathy phenotype in quarter horse-related breeds is modified by the presence of an RYR1 mutation.
abstract: In this study we examined a family of Quarter Horses with Polysaccharide Storage Myopathy (PSSM) with a dominant mutation in the skeletal muscle glycogen synthase (GYS1) gene. A subset of horses within this family had a more severe and occasionally fatal PSSM phenotype. The purpose of this study was to identify a modifying gene(s) for the severe clinical phenotype. A genetic association analysis was used to identify RYR1 as a candidate modifying gene. A rare, known equine RYR1 mutation, associated with malignant hyperthermia (MH), was found to segregate in this GYS1 PSSM family. Retrospective analysis of patient records (n=179) demonstrated that horses with both the GYS1 and RYR1 mutations had a more severe clinical phenotype than horses with the GYS1 mutation alone. A treadmill trial (n=8) showed that serum creatine kinase activity was higher and exercise intolerance greater in horses with both mutations compared to the GYS1 mutation alone.
authors.affiliation: Department of Veterinary Population Medicine, University of Minnesota College of Veterinary Medicine, 225 VMC, 1365 Gortner Avenue, St. Paul, MN 55108, USA. mccu0173@umn.edu
authors.forename: M E
authors.initials: ME
authors.lastname: McCue
authors.forename: S J
authors.initials: SJ
authors.lastname: Valberg
authors.forename: M
authors.initials: M
authors.lastname: Jackson
authors.forename: L
authors.initials: L
authors.lastname: Borgia
authors.forename: M
authors.initials: M
authors.lastname: Lucio
authors.forename: J R
authors.initials: JR
authors.lastname: Mickelson
mesh_terms: D000818:Animals; D004252:DNA Mutational Analysis; D005080:Exercise Test; D017079:Exercise Tolerance / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D006003:Glycogen / Q000378:metabolism; D006008:Glycogen Storage Disease / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D006006:Glycogen Synthase / Q000235:genetics; D006734:Horse Diseases / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006736:Horses; D040582:Inheritance Patterns / Q000235:genetics; D008297:Male; D018908:Muscle Weakness / Q000235:genetics / Q000473:pathology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics / Q000473:pathology / Q000662:veterinary*; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D012189:Retrospective Studies; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics*
chemical_list: D019837:Ryanodine Receptor Calcium Release Channel; D006003:Glycogen; D006006:Glycogen Synthase