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 metabol ic disorder, is caused by a deficiency in glucose-6-phosphatase (G6Pas e). 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 110.1 in exon 5, change the rest riction sites for the enzymes Fok I and Hinc II. Family study revealed that both parents were heterozygous carriers: the father with a mutan t G6Pase allele at exon 2 and the mother with another mutant G6Pase al lele at exon 5. This paper deals with a prenatal diagnosis on the fetu s of this family who is at risk of type Ia GSD. Genomic DNA was extrac ted from a chorionic villus biopsy sampled at the tenth week of gestat ion. Exons 2 and 5 of the G6Pase gene were amplified by the polymerase chain reaction (PCR) followed by restriction enzyme digestion and dir ect sequence analysis. DNA analysis indicated that the fetus was a het erozygous carrier of type Ia GSD with a mutant G6Pase allele at exon 2 and a normal G6Pase allele al exon 5. The diagnosis was further confi rmed by the same method with cultured amniocytes and with a blood samp le after the baby was born. This is the first report of prenatal carri er detection of type Ia GSD at the gene level.