Expanding the scope of noninvasive prenatal testing: detection of fetal microdeletion syndromes

• Published in: American journal of obstetrics and gynecology Vol. 212; no. 3; pp. 332.e1 - 332.e9
• Main Authors: Wapner, Ronald J., MD, Babiarz, Joshua E., PhD, Levy, Brynn, MSc (Med), PhD, Stosic, Melissa, MS, Zimmermann, Bernhard, PhD, Sigurjonsson, Styrmir, PhD, Wayham, Nicholas, BS, Ryan, Allison, PhD, Banjevic, Milena, PhD, Lacroute, Phil, PhD, Hu, Jing, PhD, Hall, Megan P., PhD, Demko, Zachary, PhD, Siddiqui, Asim, PhD, Rabinowitz, Matthew, PhD, Gross, Susan J., MD, Hill, Matthew, PhD, Benn, Peter, DSc
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2015
• Subjects: Algorithms; Chromosome Deletion; Chromosome Disorders - diagnosis; Chromosome Disorders - genetics; False Positive Reactions; Female; Genetic Testing - methods; Humans; Maternal Serum Screening Tests; microdeletion; Multiplex Polymerase Chain Reaction; noninvasive prenatal testing; Obstetrics and Gynecology; Polymorphism, Single Nucleotide; Predictive Value of Tests; Pregnancy; Reproducibility of Results; Sequence Analysis, DNA; single-nucleotide polymorphism; Syndrome; single-nucleotide polymorphism; noninvasive prenatal testing; microdeletion
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2014.11.041

Objective The purpose of this study was to estimate the performance of a single-nucleotide polymorphism (SNP)–based noninvasive prenatal test for 5 microdeletion syndromes. Study Design Four hundred sixty-nine samples (358 plasma samples from pregnant women, 111 artificial plasma mixtures) were amplified with the use of a massively multiplexed polymerase chain reaction, sequenced, and analyzed with the use of the Next-generation Aneuploidy Test Using SNPs algorithm for the presence or absence of deletions of 22q11.2, 1p36, distal 5p, and the Prader-Willi/Angelman region. Results Detection rates were 97.8% for a 22q11.2 deletion (45/46) and 100% for Prader-Willi (15/15), Angelman (21/21), 1p36 deletion (1/1), and cri-du-chat syndromes (24/24). False-positive rates were 0.76% for 22q11.2 deletion syndrome (3/397) and 0.24% for cri-du-chat syndrome (1/419). No false positives occurred for Prader-Willi (0/428), Angelman (0/442), or 1p36 deletion syndromes (0/422). Conclusion SNP-based noninvasive prenatal microdeletion screening is highly accurate. Because clinically relevant microdeletions and duplications occur in >1% of pregnancies, regardless of maternal age, noninvasive screening for the general pregnant population should be considered.