Disease relevance of PYGM

• Cloning of bovine muscle glycogen phosphorylase cDNA and identification of a mutation in cattle with myophosphorylase deficiency, an animal model for McArdle's disease [1].
• Genetic defects of myophosphorylase in humans cause a metabolic myopathy (McArdle's disease) characterized by exercise intolerance, cramps, and recurrent myoglobinuria [1].
• Myophosphorylase deficiency associated with rhabdomyolysis and exercise intolerance in 6 related Charolais cattle [2].
• Myophosphorylase deficiency (glycogen storage disease Type V) in a herd of Charolais cattle in New Zealand: confirmation by PCR-RFLP testing [3].

High impact information on PYGM

• In the cDNA fragments amplified by RT-PCR from muscle RNA of the cattle with myophosphorylase deficiency, we identified a C-to-T substitution, changing an encoded arginine (CGG) to tryptophan (TGG) at codon 489 [1].
• To define the molecular genetic error in the cattle, we cloned and sequenced the wild-type bovine myophosphorylase cDNA [1].
• Improvements to restriction fragment length polymorphism (RFLP)-based genotyping assays currently used for detection of mutations responsible for bovine ferrochelatase and myophosphorylase deficiencies, and equine hyperkalemic periodic paralysis (HYPP) are described [4].
• In normal diaphragmatic muscle, Hsp70 binds several proteins involved in energy metabolism including glycogen phosphorylase (PYGM) [5].
• A segment of the myophosphorylase gene containing the mutation site was amplified by polymerase chain reaction assays, and the genotype (normal vs affected allele) was determined by using restriction enzyme and agarose gel electrophoretic analysis [6].

Biological context of PYGM

• RESULTS: The 3 myophosphorylase genotypes (homozygous normal, homozygous affected, and heterozygous) could be readily identified [6].
• OBJECTIVE: To develop a simple test for the determination of genetic susceptibility to myophosphorylase deficiency in Charolais cattle [6].
• Myophosphorylase deficiency in cattle is a muscle disease induced by a C-->T point mutation in codon 489 of the myophosphorylase gene, which until now has only been diagnosed in the Charolais breed [7].
• A calf of double muscled phenotype was suspected of suffering from myophosphorylase deficiency based on typical symptoms, i.e. brown-coloured, transparent urine, occurring after exercise; exercise intolerance; symptoms of pain; and an elevated level of plasma creatine kinase [7].

Associations of PYGM with chemical compounds

• Experimentally induced GSD-like conditions have been described in the rat (Acarbose-induced GSD II-like conditions, iodoacetate-induced symptoms of myophosphorylase (GSD V) and myophosphofructokinase (GSD VII) deficiency) and the chicken (ochratoxin A-induced symptoms of cyclic AMP-dependent protein kinase deficiency) [8].

References