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Am J Hum Genet. Apr 1998; 62(4): 785–791.
PMCID: PMC1377030

Mutations in the liver glycogen phosphorylase gene (PYGL) underlying glycogenosis type VI.


Deficiency of glycogen phosphorylase in the liver gives rise to glycogen-storage disease type VI (Hers disease; MIM 232700). We report the identification of the first mutations in PYGL, the gene encoding the liver isoform of glycogen phosphorylase, in three patients with Hers disease. These are two splice-site mutations and two missense mutations. A mutation of the 5' splice-site consensus of intron 14 causes the retention of intron 14 and the utilization of two illegitimate 5' splice sites, whereas a mutation of the 3' splice-site consensus of intron 4 causes the skipping of exon 5. Two missense mutations, N338S and N376K, both cause nonconservative replacements of amino acids that are absolutely conserved even in yeast and bacterial phosphorylases. We also report corrections of the PYGL coding sequence, sequence polymorphisms, and a partial PYGL gene structure with introns in the same positions as in PYGM, the gene of the muscle isoform of phosphorylase. Our findings demonstrate that PYGL mutations cause Hers disease, and they may improve laboratory diagnosis of deficiencies of the liver phosphorylase system.

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  • Aperlo C, Boulukos KE, Sage J, Cuzin F, Pognonec P. Complete sequencing of the murine USF gene and comparison of its genomic organization to that of mFIP/USF2. Genomics. 1996 Nov 1;37(3):337–344. [PubMed]
  • Bartram C, Edwards RH, Beynon RJ. McArdle's disease-muscle glycogen phosphorylase deficiency. Biochim Biophys Acta. 1995 Aug 15;1272(1):1–13. [PubMed]
  • Burke J, Hwang P, Anderson L, Lebo R, Gorin F, Fletterick R. Intron/exon structure of the human gene for the muscle isozyme of glycogen phosphorylase. Proteins. 1987;2(3):177–187. [PubMed]
  • Burwinkel B, Maichele AJ, Aagenaes O, Bakker HD, Lerner A, Shin YS, Strachan JA, Kilimann MW. Autosomal glycogenosis of liver and muscle due to phosphorylase kinase deficiency is caused by mutations in the phosphorylase kinase beta subunit (PHKB). Hum Mol Genet. 1997 Jul;6(7):1109–1115. [PubMed]
  • Burwinkel B, Moses SW, Kilimann MW. Phosphorylase-kinase-deficient liver glycogenosis with an unusual biochemical phenotype in blood cells associated with a missense mutation in the beta subunit gene (PHKB). Hum Genet. 1997 Dec;101(2):170–174. [PubMed]
  • Burwinkel B, Shin YS, Bakker HD, Deutsch J, Lozano MJ, Maire I, Kilimann MW. Mutation hotspots in the PHKA2 gene in X-linked liver glycogenosis due to phosphorylase kinase deficiency with atypical activity in blood cells (XLG2). Hum Mol Genet. 1996 May;5(5):653–658. [PubMed]
  • Burwinkel B, Shiomi S, Al Zaben A, Kilimann MW. Liver glycogenosis due to phosphorylase kinase deficiency: PHKG2 gene structure and mutations associated with cirrhosis. Hum Mol Genet. 1998 Jan;7(1):149–154. [PubMed]
  • Crerar MM, Karlsson O, Fletterick RJ, Hwang PK. Chimeric muscle and brain glycogen phosphorylases define protein domains governing isozyme-specific responses to allosteric activation. J Biol Chem. 1995 Jun 9;270(23):13748–13756. [PubMed]
  • Dahan N, Baussan C, Moatti N, Lemonnier A. Use of platelets, mononuclear and polymorphonuclear cells in the diagnosis of glycogen storage disease type VI. J Inherit Metab Dis. 1988;11(3):253–260. [PubMed]
  • David ES, Crerar MM. Quantitation of muscle glycogen phosphorylase mRNA and enzyme amounts in adult rat tissues. Biochim Biophys Acta. 1986 Jan 15;880(1):78–90. [PubMed]
  • HERS HG. Etudes enzymatiques sur fragments hépatiques; application à la classification des glycogénoses. Rev Int Hepatol. 1959;9(1):35–55. [PubMed]
  • Hudson JW, Golding GB, Crerar MM. Evolution of allosteric control in glycogen phosphorylase. J Mol Biol. 1993 Dec 5;234(3):700–721. [PubMed]
  • Koster JF, Slee RG, Daegelen D, Meienhofer MC, Dreyfus JC, Niermeyer MF, Fernandes J. Isoenzyme pattern of phosphorylase in white blood cells and fibroblasts from patients with liver phosphorylase deficiency. Clin Chim Acta. 1976 May 17;69(1):121–125. [PubMed]
  • Lederer B, Stalmans W. Human liver glycogen phosphorylase. Kinetic properties and assay in biopsy specimens. Biochem J. 1976 Dec 1;159(3):689–695. [PMC free article] [PubMed]
  • Lederer B, Van Hoof F, Van den Berghe G, Hers H. Glycogen phosphorylase and its converter enzymes in haemolysates of normal human subjects and of patients with type VI glycogen-storage disease. A study of phosphorylase kinase deficiency. Biochem J. 1975 Apr;147(1):23–35. [PMC free article] [PubMed]
  • Maichele AJ, Burwinkel B, Maire I, Søvik O, Kilimann MW. Mutations in the testis/liver isoform of the phosphorylase kinase gamma subunit (PHKG2) cause autosomal liver glycogenosis in the gsd rat and in humans. Nat Genet. 1996 Nov;14(3):337–340. [PubMed]
  • Maire I, Baussan C, Moatti N, Mathieu M, Lemonnier A. Biochemical diagnosis of hepatic glycogen storage diseases: 20 years French experience. Clin Biochem. 1991 Apr;24(2):169–178. [PubMed]
  • Newgard CB, Littman DR, van Genderen C, Smith M, Fletterick RJ. Human brain glycogen phosphorylase. Cloning, sequence analysis, chromosomal mapping, tissue expression, and comparison with the human liver and muscle isozymes. J Biol Chem. 1988 Mar 15;263(8):3850–3857. [PubMed]
  • Newgard CB, Nakano K, Hwang PK, Fletterick RJ. Sequence analysis of the cDNA encoding human liver glycogen phosphorylase reveals tissue-specific codon usage. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8132–8136. [PMC free article] [PubMed]
  • van den Berg IE, van Beurden EA, de Klerk JB, van Diggelen OP, Malingré HE, Boer MM, Berger R. Autosomal recessive phosphorylase kinase deficiency in liver, caused by mutations in the gene encoding the beta subunit (PHKB). Am J Hum Genet. 1997 Sep;61(3):539–546. [PMC free article] [PubMed]
  • Vorgerd M, Kubisch C, Burwinkel B, Reichmann H, Mortier W, Tettenborn B, Pongratz D, Lindemuth R, Tegenthoff M, Malin JP, et al. Mutation analysis in myophosphorylase deficiency (McArdle's disease). Ann Neurol. 1998 Mar;43(3):326–331. [PubMed]

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