Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis.
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.
McCue
Molly E
ME
Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St Paul, MN 55108, USA. mccu0173@umn.edu
Valberg
Stephanie J
SJ
Miller
Michael B
MB
Wade
Claire
C
DiMauro
Salvatore
S
Akman
Hasan O
HO
Mickelson
James R
JR
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D005787:Gene Frequency; D016678:Genome; D006008:Glycogen Storage Disease / Q000201:enzymology / Q000235:genetics / Q000662:veterinary*; D006006:Glycogen Synthase / Q000235:genetics* / Q000378:metabolism*; D006239:Haplotypes; D006734:Horse Diseases / Q000201:enzymology* / Q000235:genetics*; D006736:Horses; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide
D006006:Glycogen Synthase