血友病基因携带孕妇258例产前诊断结果分析  

Prenatal diagnosis results of 258 pregnant women carrying hemophilia gene

作　　者：肖超群[1] 王克[1] 杨芳[1] 杨土银[1] 李思思[1] 王志坚[1] 

机构地区：[1]南方医科大学南方医院妇产科产前诊断中心,广东广州510515

出　　处：《广东医学》2018年第4期521-523,共3页Guangdong Medical Journal

基　　金：广东省科技计划项目(编号:2015B010106002)

摘　　要：目的通过分析血友病基因携带孕妇的产前诊断结果,评价多种直接基因诊断方法联合使用对血友病基因检测的价值。方法对产前诊断中心行产前诊断的258例血友病基因携带孕妇,联合应用LDPCR、MLPA、基因测序方法对胎儿基因进行直接检测。孕周为11~13周胎儿检测样本通过绒毛吸取术获得,孕周18~28周胎儿检测样本通过羊水穿刺获得。统计致病基因胎儿阳性率、各检测方法的阳性检出率。结果258例血友病基因携带者中,血友病A为225例(87.2%),血友病B为33例(12.8%)。产前诊断胎儿中血友病A基因诊断阳性84例(37.3%),血友病B基因诊断阳性5例(38.6%)。绒毛穿刺131例(50.8%),羊水穿刺127例(49.2%)。穿刺术均无不良事件发生。84例血友病A基因检测阳性病例中,F8基因内含子22倒位39例(46.4%),内含子1倒位4例(4.8%),基因大片段缺失3例(3.6%),基因点突变38例(45.2%)。5例血友病B基因检测阳性者,F9基因4号外显子G-A点突变2例、5号外显子G碱基丢失2例、2号内含子5'端第4碱基A-T突变1例。基因检测阴性胎儿出生后随访1~2年,无血友病发生。结论LD-PCR、MLPA和直接基因测序法联合使用,能对血友病基因进行有效检测,值得临床推广。Objective To evaluate the value of the combined method of several genetic testing for hemophilia, through analyzing the prenatal diagnosis results of pregnant hemophilia gene carriers. Methods Genetic tests were done in 258 carriers of hemophilia gene who had their prenatal diagnosis, using combined LD - PCR, MIPA, and gene sequen- cing. At the gestation age of 11 - 13 weeks, DNA tests of fetus were done by chorionic aspiration. At the gestation age of 18 -28 weeks, fetus had their test by amniocentesis. Positive rates of genetic test and of each method were calculated. Results Among 258 cases of pregnant hemophilia carriers, Hemophilia A accounted for 225 cases （ 87.2% ） , while he- mophilia B for 33 cases （ 12. 8% ）. In the prenatal diagnosis, positive hemophilia A was in 84 cases （37.3%）, while he- mophilia B in 5 cases （38.6%）. No adverse event was reported in 131 cases of chorionic aspiration and 127 cases of am- nioeentesis. In 84 cases of hemophilia A, 39 were lntron 22 inversion in F8 gene, 4 were Intron 1 inversion, 3 with large deletion in genes, and 38 with spot mutation. Among 5 patients with hemophilia B, 2 had G - A spot mutation in Exon 4, 2 had lost G base in 5 Exon, and 1 had A -T mutation in 4th base of 5 ＇side of Intron 5. Fetus tested negative were fol- lowed up for 1 - 2 years. No false negative was reported. Conclusion Combination of LD - PCR, MLPA and gene se- quence can serve as an effective diagnosis for hemophilia.

关 键 词：血友病基因 产前诊断 长距离PCR 多重连接依赖性探针扩增技术 基因测序 

分 类 号：R714.5[医药卫生—妇产科学]