【摘要】 目的探讨羊水细胞低密度脂蛋白受体(low density lipoprotein receptor,LDLR)基因突变分析在家族性高胆固醇血症(familial hypercholesterolemia,FH)产前诊断中的应用价值。方法 3例曾生育FH重症患儿并再次妊娠的妇女及其核心家系成员,提取其外周血基因组DNA,筛查LDLR基因突变;于妊娠16～20周在超声引导下行羊膜腔穿刺术抽取羊水,提取胎儿脱落细胞DNA,分别对家系存在的LDLR基因突变进行检测,判断胎儿是否为重症FH。结果 3个家系均符合FH诊断,并分别在LDLR基因检测到2个互不相同的杂合突变位点;胎儿LDLR基因核苷酸序列分析证实,1号家系胎儿仅携带该家系1个突变位点判断为杂合(轻症),2号家系胎儿携带该家系2个突变位点判断为复合杂合(重症),3号家系胎儿未检到该家系的突变位点推测为正常个体。结论 FH孕妇羊水脱落细胞LDLR基因分析安全有效,可尽早发现FH纯合子患儿。更多还原

【Abstract】 Objective To evaluate the value of low density lipoprotein receptor(LDLR) gene mutation of amniotic cell to the prenatal diagnosis of familial hypercholesterolemia(FH).Methods Three women delivering severe FH children and their core family pedigrees were extracted genomic DNA from peripheral blood and screened LDLR gene mutations.Amniotic fluid was drawn through amniocentesis under ultrasound in 16 to 20 weeks of re-pregnancy,and fetal DNA was extracted to detect the LDLR gene exons with family mutation and to determine whether the fetuses were severe FH.Results All the family pedigrees were accorded with the diagnostic standard of FH,and two different LDLR gene heterozygous mutations were detected in each family.The results of fetal LDLR gene DNA sequencing analysis showed that fetus in the first family carried one of family mutations and was assessed FH heterozygous(mild),fetus in the second family carried two of family mutations and was assessed compound heterozygous(severe),and fetus in the third family was not detected any LDLR mutations of the family and was assessed normal individual.Conclusion LDLR gene DNA sequencing analysis of amniotic cells in FH families is safe and effective for FH pregnant women,and it can detect FH homozygous fetus early.更多还原