Genome-wide normalized score: a novel algorithm to detect fetal trisomy 21 during non-invasive prenatal testing

Abstract

(GWNS, NCV,

Detection of 22q11.2 microduplication by cell‐free DNA screening and chromosomal microarray in fetus with multiple anomalies

“…However, it is still challenging to regularly detect microduplications as there is only a 1.5‐fold change in copy number (3:2) instead of a 2‐fold change (1:2) that occurs during microdeletions. In our case, we identified successfully two microduplications involving chromosomes 11q and 22q11.2 using the Z‐ score algorithm and our own GWNS algorithm3, and the results were further confirmed by CMA. Based on the results of parental and fetal karyotyping, we delineated a causal interpretation of reciprocal translocation involving 11q23 and 22q11.2.…”

Noninvasive prenatal testing using a novel analysis pipeline to screen for all autosomal fetal aneuploidies improves pregnancy management

“…16 MPS for aneuploidy detection applies counting statistics to millions of sequencing reads to identify subtle changes in the small percentage of fetal DNA present in the total cell-free DNA isolated from maternal plasma. 17,18 An increase or decrease in the number of normalized sequencing reads, typically converted to a 'z-score', 18 a 'normalized chromosome value', 13 genome-wide normalized score 19 or by 'withinsample copy number aberration detector' 20 is indicative of aneuploidy for the respective chromosome. Despite the high accuracy of current NIPT testing, a baseline false-positive and false-negative rate remains.…”

Confined placental mosaicism of double trisomies 9 and 21: discrepancy between non-invasive prenatal testing, chorionic villus sampling and postnatal confirmation

“…The fetal fraction of the cell-free DNA in this case was estimated as 13% by our in-house NIPT, and thus, theoretically, the fetal fraction of the trisomy-21 cells in the maternal plasma would be 4.6% (i.e. 13% × 35%), which is close to the lowest limit (4-5%) of the fetal fraction of cell-free DNA feasible for NIPT 3 . Similarly, the actual fraction of the fetal DNA in the maternal plasma may not reflect the percentage of the trisomy-21 cell line observed when karyotyping the villus samples, which can also lead to a negative NIPT result.…”

“…No significant anomaly was noted except oligohydramnios ( Figure 1). Repeated NIPT with the genome-wide normalized score test 3 , performed by our laboratory, also indicated a high risk for trisomy 9 (P < 0.0001). Interphase fluorescence (Figure 2a).…”