GLUCOSE-6-PHOSPHATASE GENE (727G-]T) SPLICING MUTATION IS PREVALENT IN HONG-KONG CHINESE PATIENTS WITH GLYCOGEN-STORAGE-DISEASE TYPE 1A

Glycogen storage disease type 1a (GSD1a) is an autosomal recessive met abolic disorder caused by a deficiency in glucose-6-phosphatase (G6Pas e). We analyzed the G6Pase genes of two unrelated Chinese families wit h GSD1a, DNA sequencing of all five exons and the exon-intron boundari es revealed a G --> T transversion at nucleotide 727 (7276 --> T) in e xon 5, which has previously been reported to cause abnormal splicing. In one family. the subject and her affected sister were confirmed to b e homozygous for this mutation and their parents to be heterozygotes. In the other family, the proband was identified to be heterozygous for this mutation, and a novel mutation, the 341delG in exon 2, was ident ified. This mutation alters the reading frame and creates a stop codon TAA 15 codons downstream from the mutation, resulting in a truncated protein. Family studies revealed that the father was heterozygous for the 7276 --> T mutation and that the mother was heterozygous for the 3 41delG mutation. This is the first time that the 7276 --> T mutation h as been found in Chinese patients or outside Japan. Since we only test ed two GSD1a families and found 7276 --> T in both, we believe that th is mutation may also be prevalent in our local Chinese population. To investigate allele frequencies, we screened 385 Chinese healthy volunt eers and found two asymptomatic carriers. Our findings suggest that th e 7276 --> mutation is indeed prevalent in Hong Kong.