IDENTIFICATION OF A POINT MUTATION (G727T) IN THE GLUCOSE-6-PHOSPHATASE GENE IN JAPANESE PATIENTS WITH GLYCOGEN-STORAGE-DISEASE TYPE 1A, AND CARRIER SCREENING IN HEALTHY-VOLUNTEERS

Glycogen storage disease type la (GSD la) is an autosomal recessive me tabolic disorder caused by a deficiency in glucose-6-phosphatase (G6Pa se). We analyzed the G6Pase gene of two unrelated Japanese families wi th GSD la. DNA sequencing of all five exons and exon-intron junctions revealed a G-to-T transversion at nucleotide 727 (G727T) in exon 5, wh ich has been previously reported to cause abnormal splicing. Family st udies using mismatch PCR showed that three patients were homozygous fo r the G727T mutation, while the parents were heterozygous. To investig ate allele frequencies, we screened 216 Japanese healthy volunteers an d found one asymptomatic carrier. Our findings suggest that the G727T mutation may be prevalent in Japan.