GENETIC-ANALYSIS OF THE GLUCOSE-6-PHOSPHATASE MUTATION OF TYPE 1A GLYCOGEN-STORAGE-DISEASE IN A CHINESE FAMILY

Type 1a glycogen storage disease (GSD) is an autosomal recessive metab olic disorder caused by a deficiency in glucose-6-phosphatase (G6Pase) . Polymerase chain reaction (PCR) and nucleotide sequence analysis wer e used to identify the location and nature of mutations at the G6Pase locus in two siblings affected with type 1a GSD. Both patients are com pound heterozygotes with two different single nucleotide substitutions in the two G6Pase alleles. a guanine to adenine transition was identi fied at base position 327 in the exon 2, converting an arginine to a h istidine at codon 83. The second substitution was a thymine to adenine transversion at base position 1101 in the exon 5, converting an isole ucine to an asparagine at codon 341. Family study reveals that both pa rents are heterozygous carriers: the father with a mutant G6Pase allel e at exon 2, the mother with another mutant G6Pase allele at exon 5. T his is the first family study in Taiwan on type 1a GSD identified by m olecular analysis. The mutations identified herein are novel substitut ions in the G6Pase gene. In addition, an adenine to guanine substituti on was observed at base position 653 in the exon 5 of G6Pase gene in b oth sibling patients and their parents, as well as in 15 normal Chines e subjects and three normal Caucasian subjects.