title: Mutations in the glucose-6-phosphatase gene that cause glycogen storage disease type 1a.
abstract: Glycogen storage disease (GSD) type 1a is caused by the deficiency of D-glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. Despite both a high incidence and morbidity, the molecular mechanisms underlying this deficiency have eluded characterization. In the present study, the molecular and biochemical characterization of the human G6Pase complementary DNA, its gene, and the expressed protein, which is indistinguishable from human microsomal G6Pase, are reported. Several mutations in the G6Pase gene of affected individuals that completely inactivate the enzyme have been identified. These results establish the molecular basis of this disease and open the way for future gene therapy.
authors.affiliation: Human Genetics Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
authors.forename: K J
authors.initials: KJ
authors.lastname: Lei
authors.forename: L L
authors.initials: LL
authors.lastname: Shelly
authors.forename: C J
authors.initials: CJ
authors.lastname: Pan
authors.forename: J B
authors.initials: JB
authors.lastname: Sidbury
authors.forename: J Y
authors.initials: JY
authors.lastname: Chou
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D005952:Glucose-6-Phosphatase / Q000235:genetics* / Q000378:metabolism; D005953:Glycogen Storage Disease Type I / Q000201:enzymology / Q000235:genetics*; D006031:Glycosylation; D006801:Humans; D008099:Liver / Q000201:enzymology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D005952:Glucose-6-Phosphatase