Molecular and Genetic Medicine

Clinical Utility of High-Throughput Sequencing for Pregnancies with Ultrasound Anomalies in Southern China

Abstract

Zhao P1-5, Lin L, Wang H and Lan L

We evaluated the clinical utility of high-throughput sequencing for fetal abnormalities detected with ultrasound examination. This study included pregnant women who were at risk for fetal aneuploidy with or without ultrasonography abnormalities, and who underwent invasive surgery. High-throughput sequencing was used for cell-free fetal DNA analysis, and some positive results were compared with conventional karyotyping. This study involved 971 pregnancies, cell-free fetal DNA identified 15 of 18 (83.33%) as fetal Down syndrome, 4 of 5 (80.00%) as trisomy 18, and 0 of 1 (0.00%) as trisomy 13. Comparing high-throughput sequencing results with conventional fetal karyotypes, we observed that sequencing revealed sub-chromosomal duplications or deletions, but results of karyotyping showed aberrations in chromosome structure or a normal karyotype. One chromosomal balanced translocation was inherited from the mother, another one chromosomal abnormalities was inherited from the father. When fetal chromosomal abnormalities were found by ultrasound abnormalities, non-invasive prenatal testing should not be recommended for the genetic evaluation. Invasive procedure should be first offered to the pregnant woman when abnormal nuchal translucency or other ultrasound abnormalities were found. During invasive prenatal diagnostic testing, fetal chromosomal anomalies should be evaluated by high-throughput sequencing combining with conventional karyotyping.