摘要
目的探讨中国人Ia型糖原累积病简便、快速、准确的产前诊断方法。方法通过限制性内切酶图谱分析了葡萄糖6磷酸酶(glucose-6-phosphatase,G6Pase)基因727G→T和R83H的突变,并结合1176位点单核苷酸多态性连锁分析,对3个Ia型糖原累积病家系进行了基因诊断和产前诊断。对发现的突变及1176位点多态性用DNA测序证实。结果3个家系先证者G6Pase基因的2个等位基因均携带727G→T突变,分别来自其父母。家系1和3胎儿为727G→T突变杂合子;家系2胎儿不携带该突变。1176位点单核苷酸多态性分析显示,3名胎儿1176位点单核苷酸多态性与3名先证者不同。DNA直接测序结果与限制性内切酶图谱分析结果相符。家系1和家系2胎儿已出生,并证实与产前诊断结果相符。结论通过限制性内切酶酶切法筛查727G→T和R83H突变结合1176位点单核苷酸多态性连锁分析可简便、快速、准确地诊断和产前诊断Ia型糖原累积病。
Objective To develop and evaluate a simple, fast and accurate prenatal diagnosis method for glycogen storage disease Ia (GSD Ia) in Chinese. Methods This study involved 3 unrelated families. Genomic DNA samples were extracted from the blood of three GSD Ia patients and their parents, from the amniocytes of 3 fetuses and the blood of 2 newborns. By the way of restriction enzyme analysis, the screening for 727G→T and R83H mutations of glucose-6-phosphatase gene was carried out in conjunction with 1176 nucleotide polymorphism linkage analysis so as to make the gene and prenatal diagnosis of 3 GSD Ia families. Direct DNA sequencing of the corresponding PCR products was used to confirm the unveiled mutations and 1176 nucleotide polymorphism. Results Three probands were homozygotes for the 727G→T mutation and their parents were heterozygotes for this mutation. The fetuses of family 1 and 3 were heterozygotes for the 727G→T mutation, whereas the fetus of family 2 did not carry this mutation. The 1176 nucleotide polymorphisms of 3 fetuses were different from those of the corresponding probands. The prenatal diagnoses of family 1 and 2 were confirmed by the postnatal biochemical and molecular studies. Conclusion These findings suggest that the screening for 727G→T and R83H mutations in conjunction with the 1176 polymorphism linkage analysis be a simple, fast and accurate method for gene and prenatal diagnosis of GSD Ia in Chinese.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2005年第1期44-48,共5页
Chinese Journal of Medical Genetics
基金
上海市青年科技启明星计划(03QC14023)~~
