Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis

Molly E McCue, Stephanie J Valberg, Michael B. Miller, Claire Wade, Salvatore DiMauro, Hasan O. Akman, James R Mickelson

Research output: Contribution to journalArticlepeer-review

153 Scopus citations


Polysaccharide storage myopathy (PSSM) is a novel glycogenosis in horses characterized by abnormal glycogen accumulation in skeletal muscle and muscle damage with exertion. It is unlike glycogen storage diseases resulting from known defects in glycogenolysis, glycolysis, and glycogen synthesis that have been described in humans and domestic animals. A genome-wide association identified GYS1, encoding skeletal muscle glycogen synthase (GS), as a candidate gene for PSSM. DNA sequence analysis revealed a mutation resulting in an arginine-to-histidine substitution in a highly conserved region of GS. Functional analysis demonstrated an elevated GS activity in PSSM horses, and haplotype analysis and allele age estimation demonstrated that this mutation is identical by descent among horse breeds. This is the first report of a gain-of-function mutation in GYS1 resulting in a glycogenosis.

Original languageEnglish (US)
Pages (from-to)458-466
Number of pages9
Issue number5
StatePublished - May 2008

Bibliographical note

Funding Information:
Funding for this work was provided by the American Quarter Horse Association (Genetic Analysis of Glycogen Storage Disorders in Quarter Horses), the Morris Animal Foundation (DO5EQ-028 Horse Genomics: Linear Mapping and Microarray Development), and the National Institutes of Health (NIH T32 RR018719-02 Comparative Medicine and Pathology Training, M.E. McCue, salary support).


  • Gain-of-function mutation
  • Genome-wide association
  • Glycogen storage disease
  • Glycogen synthase
  • Horse
  • Polysaccharide storage myopathy


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