Detection of fetal sex chromosome aneuploidy by massively parallel sequencing of maternal plasma DNA: initial experience in a Chinese hospital

作者：Yao, H.; Jiang, F.; Hu, H.; Gao, Y.; Zhu, Z.; Zhang, H.; Wang, Y.; Guo, Y.; Liu, L.; Yuan, Y.; Zhou, L.; Wang, J.; Du, B.; Qu, N.; Zhang, R.; Dong, Y.; Xu, H.; Chen, F.; Jiang, H.; Liu, Y.; Zhang, L.; Tian, Z.; Liu, Q.; Zhang, C.; Pan, X.; Yang, S.; Zhao, L.; Wang, W.; Liang, Z.^*

来源：Ultrasound in Obstetrics and Gynecology, 2014, 44(1): 17-24.

DOI：10.1002/uog.13361

• clinical counseling
• fetal DNA
• massively parallel sequencing
• maternal serum
• prenatal screening test
• sex chromosome aneuploidy

Objectives To evaluate the performance of a massively parallel sequencing (MPS)-based test in detecting fetal sex chromosome aneuploidy (SCA) and to present a comprehensive clinical counseling protocol for SCA-positive patients. @@@ Methods This was a retrospective study in a large patient cohort of 5950 singleton pregnancies which underwent MPS-based testing as a prenatal screening test for trisomies 21, 18 and 13, with X and Y chromosomes as secondary findings, in Southwest Hospital in China. MPS-based SCA-positive women were offered the choice of knowing whether their SCA results were positive and those who did commenced a two-stage post-test clinical counseling protocol. In Stage 1, general information about SCA was given, and women were given the option of invasive testing for confirmation of findings; in Stage 2, those who had chosen to undergo invasive testing were informed about the specific SCA affecting their fetus and their management options. @@@ Results Thirty-three cases were classified as SCA-positive by MPS-based testing. After Stage 1 of the two-stage post-test clinical counseling session, 33 (100%) of these pregnant women chose to know the screening test results, and 25 (75.76%) underwent an invasive diagnostic procedure and karyotype analysis, in one of whom karyotyping failed. In thirteen cases, karyotyping confirmed the MPS-based test results (two X0 cases, seven XXX cases, three XXY cases and one XYY case), giving a positive predictive value of 54.17% (13/24 cases confirmed by karyotyping). After post-test clinical counseling session Stage 2, seven women chose to terminate the pregnancy: one X0 case, two XXX cases, the three XXY cases and the single XYY case. Six women decided to continue with pregnancy: one X0 case and five XXX cases. @@@ Conclusion Our study showed the feasibility of clinical application of the MPS-based test in the non-invasive detection of fetal SCA. Together with a two-stage post-test clinical counseling protocol, it leads to a well-informed decision-making procedure.

• 出版日期2014-7
• 单位深圳华大生命科学研究院