G6Pase is a key enzyme in the process of glycogenolysis and gluconeogenesis, expressed mainly in the liver, kidney and small intestine, and plays an important role in maintaining normal blood glucose levels. It is located on the long arm of chromosome 17, region 2, band 1, with approximately 12.5 kb and contains 5 exons. the G6Pase protein is an endoplasmic reticulum membrane protein containing 357 amino acids and is highly hydrophobic, with 9 transmembrane units, its N-terminal located in the lumen of the endoplasmic reticulum and its C-terminal located on the plasma membrane. Before G6Pase gene cloning, prenatal diagnosis was performed by fetal liver puncture biopsy to determine G6Pase activity, which was rarely used because of the invasive nature of the test and the poor reproducibility of the enzyme activity assay [5]. In recent years, with the cloning of the G6Pase cDNA, the mutation spectrum and mutation hotspots of the G6Pase gene around the world have been gradually clarified, making prenatal diagnosis by molecular biology possible. To date, more than 70 mutations have been identified in the coding region of the G6Pase gene. Four GSD Ia families with prenatal diagnosis by mutation detection method have been reported in foreign literature [6-9]. Several common mutation types were found in populations of different ethnic and geographic origin, such as R83C and Q347X mutations are most common in Caucasians [10]. Our recent study found that the 727G→T mutation accounted for 78.85% of the total mutations in 26 Chinese patients with GSD Ia and the R83H mutation accounted for 13.46% of the total mutations in 26 patients, and the 727G→T and R83H mutations together accounted for approximately 92% of the total mutations, making them the most common hotspot mutations in the Chinese population [11]. The concentration of mutations makes it possible to carry out genetic diagnosis and prenatal diagnosis in the Chinese population by first applying restriction endonuclease profiling to screen for 727G→T and R83H mutations, and then detecting other mutations by direct DNA sequencing. It is this method that was used to rapidly clarify genetic diagnosis and prenatal diagnosis in the three families in this study. Prenatal diagnosis is one of the effective measures to prevent the occurrence of inherited metabolic diseases, and it is best to use different methods in combination to ensure accurate and rapid diagnosis. Polymorphism linkage analysis is an indirect way to perform genetic diagnosis and prenatal diagnosis by performing haploinsufficient linkage analysis with polymorphic loci or fragments within or beside genes in a specific family, and making indirect diagnosis based on polymorphic loci or fragments linked to disease-causing genes. It was found that the single nucleotide at locus 1176 in the 3′ untranslated region of G6Pase has T or C polymorphism (Genbank U01120), and our previous study found that 1176C accounts for about 46% (24/52) and 1176T accounts for 54% (28/52) of the Chinese, and the polymorphic information of this single nucleotide polymorphic locus in Chinese G6Pase gene is 12.5kb in length, and 1176T/C is only 22bp away from the last exon of G6Pase, so the chance of recombination between 1176T/C and G6Pase mutation site is negligible, which makes 1176T/C useful for prenatal diagnosis and carrier diagnosis of GSD Ia family. This makes 1176T/C of great significance for prenatal diagnosis and carrier diagnosis of GSD Ia lines. In this study, the parents of line 1 were both heterozygous for 1176T/C, the prenatal carrier was purely heterozygous for 1176C, and the fetus was heterozygous for 1176T/C. In this line, a definitive prenatal diagnosis could be made by family linkage analysis of the 1176 polymorphic locus alone. In family lines 2 and 3, the father is a 1176T/C heterozygote, the mother is a 1176C pure heterozygote, and the prenatal witness is a 1176C pure heterozygote, in this family line the 1176 locus single nucleotide polymorphism can only provide 50% of the information, i.e. a definitive prenatal diagnosis can only be made when the fetus has a 1176 locus single nucleotide polymorphism of 1176T/C, and when the fetus has a 1176 locus single nucleotide polymorphism of 1176T/C. The prenatal diagnosis could not be made when the fetal single nucleotide polymorphism at locus 1176 was 1176C pure.