-
Views
-
Cite
Cite
Tianjiao Chu, Suveyda Yeniterzi, Svetlana A. Yatsenko, Mary Dunkel, Aleksandar Rajkovic, W. Allen Hogge, David G. Peters, Cell-free nucleic acids as non-invasive biomarkers of gynecological disorders, fetal aneuploidy and constitutional maternal chromosomal mosaicism, Human Reproduction Update, Volume 21, Issue 5, September/October 2015, Pages 690–692, https://doi.org/10.1093/humupd/dmv015
Close - Share Icon Share
Extract
Sir,
We enjoyed reading the article entitled ‘Cell-free nucleic acids as non-invasive biomarkers of gynecological cancers, ovarian, endometrial and obstetric disorders and fetal aneuploidy’ by Traver et al. (2014). It is now widely accepted that massively parallel sequencing of maternal plasma DNA provides high sensitivity and specificity for non-invasive detection of fetal aneuploidy (Wang et al., 2014, 2015). However, recent studies have raised concerns about high false-positive rates of such non-invasive prenatal testing (NIPT) assays reaching up to 7% for trisomy 21 (Wang et al., 2015). One important consideration is the impact of the maternal genome as a possible cause of false-positive results, including gynecological conditions (Lau et al., 2013; Traver et al., 2014). There is also another important factor to consider; the presence of constitutional maternal chromosomal mosaicism.
We analyzed a 28-year-old primigravida who was enrolled into our research study under an IRB-approved protocol due to abnormal fetal ultrasound showing cystic hydroma at 10 weeks of gestation. NIPT using plasma DNA sequencing, coupled with the ‘Minimally Invasive Karyotyping’ (MINK) analysis algorithm (Chu et al., 2009) was performed and returned a significant P-value consistent with a gain in copy number of chromosome 21, yet the fetal karyotype was normal as determined by chorionic villus sampling (CVS) followed by classical chromosome and FISH analyses. NIPT was initially interpreted as a false-positive finding. However, we suspected there might be a biological explanation and performed high-resolution copy number variation analyses of maternal genomic DNA, CVS derived DNA and maternal plasma DNA. By comparing the affected maternal plasma and maternal genomic DNA libraries, respectively, against normal plasma and normal genomic DNA libraries, we identified a gain of ∼26% in maternal plasma and a gain of 28% in maternal genomic DNA involving the 21q11.2–q22.12 chromosome region (chr21:14 350 000–32 650 000) (Fig. 1A and B).
