VP30.01: Cell‐free DNA screening for 22q11.2DS by targeted method based on microarray quantitation in the average risk population: results from a single European laboratory

Abstract

Evaluation of the clinical performance in a single clinical laboratory of a cell-free DNA (cfDNA) screening based on targeted cfDNA analysis with microarray quantitation for 22q11.2DS applied in a population of women at average risk. Targeted cfDNA analysis using DANSR™ and FORTE™ with microarray quantitation were conducted following the protocol described by Juneau et al (2014) and Schmid et al (2017). Test results, positive predictive values, and performance characteristics were evaluated. A total 1141 samples were analysed for 22q11.2DS. Indications for the analysis was advanced maternal age (≥35y) or maternal choice (<35y) in 94.5% of the cases (n = 1078), ultrasound abnormalities in 1.4% (n = 16) and increased risk after first trimester combined test in 4.1% (n = 47). Average FF% was 11.6% ± 3.8% (min 4.1%-max 27.6%). Average gestational age was 12.5 ± 1.7 (min 10-max 32.2). In 9 samples (0.79%) test provided a no result after a second blood draw. Of the 1132 samples with a result, 7 (0.62%) had a positive result for 22q11.2DS; in 5 of them an invasive confirmatory procedure was undertaken by amniocentesis (71.4%) with microarray analysis and in 1 case the deletion was confirmed on fetal DNA. The deletion was de novo in origin and of 3Mb in size. In 3 out of the 4 cases with unconfirmed 22q11.2DS, maternal array was conducted and provided a normal result. PPV was 20% and false positive rate (FPR) considering all cases without follow-up as false positives was 0.53%. This targeted cfDNA prenatal screening for 22q11.2DS based on microarray quantitation used in a population of pregnant women at average risk provides low FPR and the PPV is in the expected range based on the results of the analytical validation. The low FPR for this cfDNA test expansion is critical when testing low-risk population as it highly impacts PPV.