title: Heterogeneous mutations in the glucose-6-phosphatase gene in Japanese patients with glycogen storage disease type Ia.
abstract: Glycogen storage disease type Ia (GSD-Ia) is an autosomal recessive disorder of glycogen metabolism caused by glucose-6-phosphatase (G6Pase) deficiency. It is characterized by short stature, hepatomegaly, hypoglycemia, hyperuricemia, and lactic acidemia. Various mutations have been reported in the G6Pase gene (G6PC). However, in Japanese patients, a g727t substitution was found to be the major cause of GSD-Ia, accounting for 20 of 22 mutant alleles [Kajihara et al., 1995], and no other mutations have been found in this population. We analyzed four Japanese GSD-Ia patients and identified three other mutations in addition to the g727t. They included two missense mutations (R83H and P257L) and one nonsense mutation (R170X). Each of the three mutations exhibited markedly decreased G6Pase activity when expressed in COS7 cells. A patient homozygous for R170X showed multiple episodes of profound hypoglycemia associated with convulsions, while P257L was associated with a mild clinical phenotype. The presence of R170X in three unrelated families may implicate that it is another important mutation in the etiology of GSD-Ia in Japanese patients. Thus, the detection of non-g727t mutations is also important in establishing the DNA-based diagnosis of GSD-Ia in this population.
authors.affiliation: Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.forename: J
authors.initials: J
authors.lastname: Akanuma
authors.forename: Y
authors.initials: Y
authors.lastname: Matsubara
authors.forename: K
authors.initials: K
authors.lastname: Fujii
authors.forename: S
authors.initials: S
authors.lastname: Kure
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Wataya
authors.forename: O
authors.initials: O
authors.lastname: Sakamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Aoki
authors.forename: M
authors.initials: M
authors.lastname: Ogasawara
authors.forename: T
authors.initials: T
authors.lastname: Ohura
authors.forename: S
authors.initials: S
authors.lastname: Miyabayashi
authors.forename: K
authors.initials: K
authors.lastname: Narisawa
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005952:Glucose-6-Phosphatase / Q000235:genetics* / Q000378:metabolism; D005953:Glycogen Storage Disease Type I / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007564:Japan; D008297:Male; D009154:Mutation; D017354:Point Mutation; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D011993:Recombinant Fusion Proteins; D004247:DNA; D005952:Glucose-6-Phosphatase; D001616:beta-Galactosidase