Validation of a SNP-based non-invasive prenatal test to detect the fetal 22q11.2 deletion in maternal plasma samples

PLoS One. 2018 Feb 23;13(2):e0193476. doi: 10.1371/journal.pone.0193476. eCollection 2018.

Abstract

Introduction: Non-invasive prenatal testing (NIPT) for aneuploidy using cell-free DNA in maternal plasma has been widely adopted. Recently, NIPT coverage has expanded to detect subchromosomal abnormalities including the 22q11.2 deletion. Validation of a SNP-based NIPT for detection of 22q11.2 deletions demonstrating a high sensitivity (97.8%) and specificity (99.75%) has been reported. We sought to further demonstrate the performance of a revised version of the test in a larger set of pregnancy plasma samples.

Methods: Blood samples from pregnant women (10 with 22q11.2-deletion‒affected fetuses and 390 negative controls) were successfully analyzed using a revised SNP-based NIPT for the 22q11.2 deletion. The sensitivity and specificity of the assay were measured.

Results: Sensitivity of the assay was 90% (9/10), and specificity of the assay was 99.74% (389/390), with a corresponding false positive-rate of 0.26%.

Discussion: The data presented in this study add to the growing body of evidence demonstrating the ability of the SNP-based NIPT to detect 22q11.2 deletions with high sensitivity and specificity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 22
  • Female
  • Genetic Testing / methods*
  • Humans
  • Mothers*
  • Plasma / metabolism*
  • Polymorphism, Single Nucleotide*
  • Pregnancy
  • Prenatal Diagnosis / methods*

Supplementary concepts

  • Chromosome 22, microdeletion 22 q11

Grants and funding

This study was funded by Natera, Inc. The funder (Natera) provided support in the form of salaries for the following authors [HR, GM, SG, NH, AR, and ZD], and played a role in all aspects of the study including designing the study, data collection and analysis, decision to publish, and preparation of the manuscript.