Two false negative cases in noninvasive prenatal testing for fetal chromosomal aneuploidies / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the limitation of non-invasive prenatal testing (NIPT) technique through analyzing two false negative cases.</p><p><b>METHODS</b>Chromosomal karyotyping analysis was performed on umbilical cord blood sample derived from case 1 at 24 weeks' gestation and peripheral blood sample derived from the neonate of case 2. Placental tissues of case 1 and peripheral blood sample of case 2 were also analyzed by high-throughput sequencing for copy number variations (CNVs).</p><p><b>RESULTS</b>For case 1, analysis of fetal umbilical cord blood sample showed a translocation type of trisomy 21, i.e., 46,XY,der(21;21)(q10;q10),+21. There were no obvious abnormalities detected at or near the center of the fetal surface and matrix surface of the placenta. High-thoroughput sequencing showed Chr13(33 840 001 - 115 100 000)×3[60%]/46,XY[40%] at the edge of the placenta, Chr13(34 080 001-115100000)×3[54%]/46,XY[46%] at the edge of placenta matrix surface, and trisomy 21 in the umbilical cord tissue. For case 2, analysis of the neonatal peripheral blood sample showed a karyotype of 46,XY,del(18)(q22), which revealed a microdeletion in chromosome 18. High-throughput sequencing of the maternal peripheral blood sample stored during pregnancy confirmed it to be chr18 (62 910 000 - 78 020 000)×1 with 15.1 Mb deletion in the fetus. The neonate was therefore diagnosed with partial monosomy of chromosome 18.</p><p><b>CONCLUSION</b>False negative results of NIPT are related with the fraction of circulating cell-free fetal DNA in the maternal serum. NIPT has limitations in detecting fetal chromosomal microdeletion and confined placenta mosaicisms. Routine ultrasound scan is necessary for pregnant women with low-risk indicated by NIPT.</p>