多种分子遗传技术应用于2例小额外标记染色体胎儿的产前筛查与诊断

目的运用多种分子遗传技术对小额外标记染色体(small supernumerary marker chromosome,sSMC)胎儿进行产前筛查和诊断,探讨各分子遗传技术的优缺点。方法对2例无创产前基因检测(non-invasive prenatal tests, NIPT)高风险胎儿的孕妇进行羊膜腔穿刺术,采集羊水标本,运用多重连接依赖探针扩增技术(multiplex ligation-dependent probe amplification,MLPA)对2例胎儿进行染色体非整倍体快速诊断,同时进行细胞培养和G显带核型分析;采用染色体微阵列技术(chromosome microarray, CMA)对胎儿1(18三体高风险)进行验证,采用MLPA技术对胎儿2(性染色体异常高风险)进行Y染色体微缺失检测。2例胎儿双亲均进行外周血G显带核型分析。结果 MLPA技术快速诊断结果为:胎儿1的18号染色体短臂部分三倍体,胎儿2携带2条正常X染色体和1条短臂缺失的Y染色体;胎儿1羊水G显带核型结果为47,XY,+Mar(胎儿1),胎儿2为47,XX,+Mar;胎儿1的CMA检测结果为arrhg19]18p11.32p11.21 (136,227-15,099)×4;胎儿2的Y染色体微缺失结果为SRY基因和生精区AZFc区缺失。2例胎儿父母双亲的外周血染色体核型均正常。结论 NIPT检测适用于sSMC胎儿的产前筛查,不同的分子遗传产前诊断技术检测sSMC胎儿各有优缺点,相互补充验证的结果可为sSMC胎儿临床遗传咨询提供更详细的信息。

Prenatal screening and diagnosis of two fetuses with small supernumerary marker chromosome by multiple molecular genetic techniques

Abstract: Objective: To investigate the advantages and disadvantages of various molecular genetic techniques in prenatal screening and diagnosis of two fetuses with small supernumerary marker chromosome (sSMC). Methods: Amniocentesis were performed on the two pregnant women with high-risk fetuses detected by noninvasive prenatal tests (NIPT), and amniotic fluid samples were collected. The multiplex ligation-dependent probe amplification (MLPA) technique was used to detect the chromosomal aneuploidy of two fetuses, and the culture of amniotic fluid cells for analyzing G-band karyotype was performed at the same time. The chromosome microarray (CMA) was used to verify the fetus with high risk of trisomy 18, and MLPA was used to detect the microdeletion of Y chromosome of the fetus with high risk of sex chromosomal abnormality. The karyotypes of two fetal parents were analyzed by the G-banding technology. Results: The rapid diagnosis results of MLPA showed that the triploid of the partial 18p was found in Fetus 1, and that two X chromosomes and one Y chromosome with deletion of Yp were found in Fetus 2. The karyotype results of amniotic fluid samples showed 47, XY + Mar in Fetus 1 and 47, XX + Mar in Fetus 2. The CMA result of Fetus 1 was arr\hg19\]18p11.32p11.21(136,227-15,099)×4. The microdeletion result of Y chromosome showed that there were deletions of SRY gene and AZFc region in Fetus 2. The karyotypes of two fetal parents were normal. Conclusion: NIPT is suitable for the prenatal screening of fetuses with sSMC. Different molecular genetic techniques have their own advantages and disadvantages in the prenatal diagnosis of sSMC. These results can be combined with each other to provide more detailed information for the clinical genetic consultation of fetuses with sSMC.