False-negative trisomy 18 non-invasive prenatal test result due to 48,XXX,+18 placental mosaicism

摘要

Analysis of cell-free DNA (cfDNA) in maternal plasma by massively parallel sequencing (MPS) has been used recently as a non-invasive prenatal testing (NIPT) approach to detect fetal chromosome aneuploidy with high sensitivity and specificity1'2. Here we report a rare placental condition of 48,XXX, trisomy 18 mosaic that led to a partially inaccurate NIPT result. The 43-year-old patient (gravida 5 para 2) with uncomplicated spontaneous pregnancy had a Down syndrome risk of 1/70 (first-trimester combined test results: pregnancy-associated plasma protein-A, 0.49 multiples of the median (MoM); free beta human chorionic gonadotropin, 1.58 MoM; and nuchal translucency, 0.66 MoM). The patient underwent NIPT at 13+2 weeks' gestation; 5 mL maternal peripheral blood was collected for cfDNA extraction, library construction and sequencing using the Illumina Hiseq 2000 platform.