Prenatal diagnosis in a Chinese family with type Ia glycogen storage disease by PCR-based genetic analysis.

Type Ia glycogen storage disease (GSD), an autosomal recessive metabolic disorder, is caused by a deficiency in glucose-6-phosphatase (G6Pase). We had previously identified the nature of the causative mutations in a Chinese family whose first two children were affected with type Ia GSD. Two different point mutations in the G6Pase gene, a guanine to adenine substitution at base position 327 in exon 2 and a thymine to adenine substitution at base position 1101 in exon 5, change the restriction sites for the enzymes Fok I and Hinc II. Family study revealed that both parents were heterozygous carriers: the father with a mutant G6Pase allele at exon 2 and the mother with another mutant G6Pase allele at exon 5. This paper deals with a prenatal diagnosis on the fetus of this family who is at risk of type Ia GSD. Genomic DNA was extracted from a chorionic villus biopsy sampled at the tenth week of gestation. Exons 2 and 5 of the G6Pase gene were amplified by the polymerase chain reaction (PCR) followed by restriction enzyme digestion and direct sequence analysis. DNA analysis indicated that the fetus was a heterozygous carrier of type Ia GSD with a mutant G6Pase allele at exon 2 and a normal G6Pase allele at exon 5. The diagnosis was further confirmed by the same method with cultured amniocytes and with a blood sample after the baby was born. This is the first report of prenatal carrier detection of type Ia GSD at the gene level.