title: Genetic analysis of the glucose-6-phosphatase mutation of type 1a glycogen storage disease in a Chinese family.
abstract: Type 1a glycogen storage disease (GSD) is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase (G6Pase). Polymerase chain reaction (PCR) and nucleotide sequence analysis were used to identify the location and nature of mutations at the G6Pase locus in two siblings affected with type 1a GSD. Both patients are compound heterozygotes with two different single nucleotide substitutions in the two G6Pase alleles. A guanine to adenine transition was identified at base position 327 in the exon 2, converting an arginine to a histidine at codon 83. The second substitution was a thymine to adenine transversion at base position 1101 in the exon 5, converting an isoleucine to an asparagine at codon 341. Family study reveals that both parents are heterozygous carriers: the father with a mutant G6Pase allele at exon 2, the mother with another mutant G6Pase allele at exon 5. This is the first family study in Taiwan on type 1a GSD identified by molecular analysis. The mutations identified herein are novel substitutions in the G6Pase gene. In addition, an adenine to guanine substitution was observed at base position 653 in the exon 5 of G6Pase gene in both sibling patients and their parents, as well as in 15 normal Chinese subjects and three normal Caucasian subjects.
authors.affiliation: Department of Medicine, Taichung Veterans General Hospital, Taiwan.
authors.forename: W J
authors.initials: WJ
authors.lastname: Lee
authors.forename: H M
authors.initials: HM
authors.lastname: Lee
authors.forename: C S
authors.initials: CS
authors.lastname: Chi
authors.forename: S G
authors.initials: SG
authors.lastname: Shu
authors.forename: L Y
authors.initials: LY
authors.lastname: Lin
authors.forename: W H
authors.initials: WH
authors.lastname: Lin
mesh_terms: D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D006580:Genetic Carrier Screening; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D005953:Glycogen Storage Disease Type I / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D013624:Taiwan
chemical_list: D005952:Glucose-6-Phosphatase