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

Am J Obstet Gynecol. 2015 Mar;212(3):332.e1-9. doi: 10.1016/j.ajog.2014.11.041. Epub 2014 Dec 2.

Abstract

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.

Keywords: microdeletion; noninvasive prenatal testing; single-nucleotide polymorphism.

Publication types

  • Evaluation Study

MeSH terms

  • Algorithms
  • Chromosome Deletion*
  • Chromosome Disorders / diagnosis*
  • Chromosome Disorders / genetics
  • False Positive Reactions
  • Female
  • Genetic Testing / methods*
  • Humans
  • Maternal Serum Screening Tests*
  • Multiplex Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Predictive Value of Tests
  • Pregnancy
  • Reproducibility of Results
  • Sequence Analysis, DNA
  • Syndrome