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J Clin Invest. 1994 December; 94(6): 2326–2329.
PMCID: PMC330061

The characterization of gene mutations for human glucose phosphate isomerase deficiency associated with chronic hemolytic anemia.


DNA was isolated from four unrelated glucose phosphate isomerase-deficient patients. Seven new mutations in the coding region were found: 247 C-->T, 671 C-->T, 818 G-->A, 833 C-->T, 1039 C-->T, 1459 C-->T, and 1483 G-->A. Three patients were compound heterozygotes, and one patient was a homozygote of 247 C-->T/247 C-->T. Six mutations were found to involve highly conserved amino acids of glucose phosphate isomerase, suggesting that these residues are crucial for the maintenance of biological activity. Two polymorphic sites were also identified, 489 A-->G and 1356 G-->C, which do not produce a change in the amino acid sequence.

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  • Blume KG, Hryniuk W, Powars D, Trinidad F, West C, Beutler E. Characterization of two new variants of glucose-phosphate-isomerase deficiency with hereditary nonspherocytic hemolytic anemia. J Lab Clin Med. 1972 Jun;79(6):942–949. [PubMed]
  • Beutler E, Sigalove WH, Muir WA, Matsumoto F, West C. Glucosephosphate-isomerase (GPI) deficiency: GPI elyria. Ann Intern Med. 1974 Jun;80(6):730–732. [PubMed]
  • Sanpitak N, Supalert Y, Chayutimonkul L, Flatz G. Combined erythrocyte phosphohexose isomerase and glucose-6-phosphate dehydrogenase deficiency. Hum Hered. 1973;23(1):83–87. [PubMed]
  • Miwa S, Nakashima Y, Oda S, Oda E, Matsumoto N. Glucosephosphate isomerase (GPI) deficiency hereditary nonspherocytic hemolytic anemia. Report of the first case found in Japanese. Nihon Ketsueki Gakkai Zasshi. 1973 Feb;36(1):65–69. [PubMed]
  • Schröter W, Koch HH, Wonneberger B, Kalinowsky W, Arnold A, Blume KG, Hüther W. Glucose phosphate isomerase deficiency with congenital nonspherocytic hemolytic anemia: a new variant (type Nordhorn). I. Clinical and genetic studies. Pediatr Res. 1974 Jan;8(1):18–25. [PubMed]
  • Arnold H, Blume KG, Löhr GW, Schröter W, Koch HH, Wonneberger B. Glucose phosphate isomerase deficiency with congenital nonspherocytic hemolytic anemia: a new variant (type Nordhorn). II. Purification and biochemical properties of the defective enzyme. Pediatr Res. 1974 Jan;8(1):26–30. [PubMed]
  • Takegawa S, Fujii H, Miwa S, Ohba Y, Yamauchi H, Miyata H. A case of congenital nonspherocytic hemolytic anemia associated with glucosephosphate isomerase (GPI) deficiency-GPI 'Kinki'. Nihon Ketsueki Gakkai Zasshi. 1983 Feb;46(1):11–17. [PubMed]
  • Merkle S, Pretsch W. Glucose-6-phosphate isomerase deficiency associated with nonspherocytic hemolytic anemia in the mouse: an animal model for the human disease. Blood. 1993 Jan 1;81(1):206–213. [PubMed]
  • Eber SW, Gahr M, Lakomek M, Prindull G, Schröter W. Clinical symptoms and biochemical properties of three new glucosephosphate isomerase variants. Blut. 1986 Jul;53(1):21–28. [PubMed]
  • Ravindranath Y, Paglia DE, Warrier I, Valentine W, Nakatani M, Brockway RA. Glucose phosphate isomerase deficiency as a cause of hydrops fetalis. N Engl J Med. 1987 Jan 29;316(5):258–261. [PubMed]
  • Fujii H, Miwa S. Recent progress in the molecular genetic analysis of erythroenzymopathy. Am J Hematol. 1990 Aug;34(4):301–310. [PubMed]
  • Arnold H. Inherited glucosephosphate isomerase deficiency. A review of known variants and some aspects of the pathomechanism of the deficiency. Blut. 1979 Dec;39(6):405–417. [PubMed]
  • Chaput M, Claes V, Portetelle D, Cludts I, Cravador A, Burny A, Gras H, Tartar A. The neurotrophic factor neuroleukin is 90% homologous with phosphohexose isomerase. Nature. 1988 Mar 31;332(6163):454–455. [PubMed]
  • Faik P, Walker JI, Redmill AA, Morgan MJ. Mouse glucose-6-phosphate isomerase and neuroleukin have identical 3' sequences. Nature. 1988 Mar 31;332(6163):455–457. [PubMed]
  • Gurney ME, Heinrich SP, Lee MR, Yin HS. Molecular cloning and expression of neuroleukin, a neurotrophic factor for spinal and sensory neurons. Science. 1986 Oct 31;234(4776):566–574. [PubMed]
  • McMorris FA, Chen TR, Ricciuti F, Tischfield J, Creagan R, Ruddle F. Chromosome assignments in man of the genes for two hexosephosphate isomerases. Science. 1973 Mar 16;179(4078):1129–1131. [PubMed]
  • Walker JI, Faik P, Morgan MJ. Characterization of the 5' end of the gene for human glucose phosphate isomerase (GPI). Genomics. 1990 Aug;7(4):638–643. [PubMed]
  • Walker JI, Layton DM, Bellingham AJ, Morgan MJ, Faik P. DNA sequence abnormalities in human glucose 6-phosphate isomerase deficiency. Hum Mol Genet. 1993 Mar;2(3):327–329. [PubMed]
  • Marchand M, Kooystra U, Wierenga RK, Lambeir AM, Van Beeumen J, Opperdoes FR, Michels PA. Glucosephosphate isomerase from Trypanosoma brucei. Cloning and characterization of the gene and analysis of the enzyme. Eur J Biochem. 1989 Sep 15;184(2):455–464. [PubMed]
  • Tekamp-Olson P, Najarian R, Burke RL. The isolation, characterization and nucleotide sequence of the phosphoglucoisomerase gene of Saccharomyces cerevisiae. Gene. 1988 Dec 15;73(1):153–161. [PubMed]

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