2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Early Performance Analysis for 22q11.2 Deletion Syndrome Detection Using a Whole-Genome Sequencing-Based Noninvasive Prenatal Screen

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This document presents an early performance analysis for the detection of 22q11.2 deletion syndrome using a whole-genome sequencing-based noninvasive prenatal screen (NIPS). The study aims to determine the efficacy of NIPS in identifying fetuses affected by 22q11.2 deletion, a common chromosomal microdeletion disorder.<br /><br />The analysis includes 13 cases that tested positive for 22q11.2 deletion using NIPS and subsequently underwent molecular diagnostic testing for confirmation. Among these cases, 12 were confirmed as true positives, and one was a false positive. The resulting positive predictive value (PPV) for 22q11.2 deletion detection using NIPS was 92.3%. The gestational age at the time of NIPS testing ranged from 10 weeks to 35 weeks.<br /><br />The study also evaluated the fetal fraction, which is the proportion of cell-free fetal DNA in the maternal blood sample. The mean fetal fraction for true positives was 21.15%, ranging from 5.9% to 36.4%. It was noted that the cohort of 22q11.2 positives had similar fetal fraction levels as other samples tested with fetal fraction amplification (FFA), suggesting that the results were not biased towards high fetal fraction samples.<br /><br />The findings suggest that NIPS using whole-genome sequencing and FFA can achieve a higher PPV for 22q11.2 deletion detection compared to previous studies. The researchers recommend the inclusion of 22q11.2 deletion screening in routine NIPS based on these results.<br /><br />The study also emphasizes the importance of early detection of microdeletion syndromes in pregnancies, as it enables appropriate management and early intervention in affected newborns. 22q11.2 deletion syndrome is estimated to occur in approximately 1 in 2,500-4,000 births and is associated with various developmental and health problems.<br /><br />The authors conclude that further data analysis and outcomes collection are ongoing to improve the certainty of these results. The study analyzed data from patients who underwent WGS-based NIPS between June 2019 and August 2022, with most samples processed after the implementation of FFA.<br /><br />Overall, the early analysis of 22q11.2 deletion screening using NIPS with FFA shows promising results and suggests its potential inclusion in routine prenatal screening for chromosomal anomalies.

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Co-Author - Summer Pierson, MS, CGC; Presenting Author - Carly Hammer, BS; Co-Author - Devika Chawla, PhD; Co-Author - Sarah Ratzel, PhD; Co-Author - Dale Muzzey, PhD; Co-Author - Katie Johansen Taber, PhD;

Meta Tag

Cell free DNA/cfDNA

Chromosomal Abnormalities

Clinical Applications of Molecular Cytogenetics

Genetic Testing

Noninvasive prenatal screening (NIPS)

Prenatal Diagnosis

Co-Author Summer Pierson, MS, CGC

Co-Author Devika Chawla, PhD

Co-Author Sarah Ratzel, PhD

Co-Author Dale Muzzey, PhD

Co-Author Katie Johansen Taber, PhD

Presenting Author Carly Hammer, BS

Keywords

22q11.2 deletion syndrome

noninvasive prenatal screen

whole-genome sequencing

chromosomal microdeletion disorder

positive predictive value

gestational age

fetal fraction

fetal DNA

microdeletion syndromes

prenatal screening