title: Molecular genetics of glycogen-storage disease type 1a in Chinese patients of Taiwan.
abstract: The mutation spectrum of the glucose 6-phosphatase (G6Pase) gene in Chinese patients with type 1a glycogen-storage disease of Taiwan was studied by PCR/RFLP, temporal temperature gradient gel electrophoresis, and direct DNA sequencing methods. In addition to the two most prevalent mutations, 727G --> T (44.4%) and R83H (36.1%), that were detected by RFLP analysis, five other mutations, 341delG, 933insAA, Q104X, I341N, and H119L were identified. The frameshift mutations (341delG and 933insAA) and the nonsense mutation (Q104X) that produce truncated proteins are predicted to be disease-causing. The missense mutation, I341N, occurring in the last transmembrane domain of the ER-bound enzyme, retains a small amount of residual activity of approximately 10%. Except for R83H, the mutations have been described only in Asians. H119L, however, is of particular interest because of the essential role of the catalytic histidine of phosphohydrolase. This amino acid is believed to be involved in the formation of the phosphoryl-enzyme intermediate during catalysis. The patient who was compound heterozygous for 727G --> T and H119L mutations had essentially no G6Pase activity in her liver biopsy. This observation is consistent with the importance of H119L in catalysis.
authors.affiliation: Institute for Molecular and Human Genetics, Georgetown University Medical Center, M4000, 3800 Reservoir Road, NW, Washington, DC 20007, USA. wonglj@gunet.georgetown.edu
authors.forename: L J
authors.initials: LJ
authors.lastname: Wong
authors.forename: W L
authors.initials: WL
authors.lastname: Hwu
authors.forename: P
authors.initials: P
authors.lastname: Dai
authors.forename: T J
authors.initials: TJ
authors.lastname: Chen
mesh_terms: D001483:Base Sequence; D002681:China; D018389:Codon, Nonsense; D004591:Electrophoresis, Polyacrylamide Gel; D016368:Frameshift Mutation; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism; D005953:Glycogen Storage Disease Type I / Q000208:ethnology* / Q000235:genetics*; D006579:Heterozygote; D006639:Histidine / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D020125:Mutation, Missense; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017434:Protein Structure, Tertiary; D012326:RNA Splicing; D017422:Sequence Analysis, DNA; D013624:Taiwan
chemical_list: D018389:Codon, Nonsense; D006639:Histidine; D010744:Phosphoric Monoester Hydrolases; D005952:Glucose-6-Phosphatase