Clinical Experience with a Single-Nucleotide Polymorphism-Based Noninvasive Prenatal Test for Five Clinically Significant Microdeletions

ABSTRACT

Single-nucleotide polymorphism (SNP)-based noninvasive prenatal testing (NIPT) can currently predict a subset of submicroscopic abnormalities associated with severe clinical manifestations. We retrospectively analyzed the performance of SNP-based NIPT in 80,449 referrals for 22q11.2 deletion syndrome and 42,326 referrals for 1p36, cri-du-chat, Prader-Willi, and Angelman microdeletion syndromes over a one-year period, and compared the original screening protocol with a revision that reflexively sequenced high-risk calls at a higher depth of read. The prevalence of these microdeletion syndromes was also estimated in the referral population. The positive predictive value of the original test was 15.7% for 22q11.2 deletion syndrome, and 5.2% for the other four disorders combined. With the revised protocol, these values increased to 44.2% for 22q11.2 and 31.7% for the others. The 0.33% false positive rate for 22q11.2 deletion syndrome decreased to 0.07% with the revised protocol. Similarly, the false positive rate for the other four disorders combined decreased from 0.56% to 0.07%. Minimal prevalences were estimated to be 1/1,255 for 22q11.2 deletion syndrome and 1/1,464 for 1p36, cri-du-chat, and Angelman syndromes combined. Our results show that these microdeletions are relatively common in the referral population, and that the performance of SNP-based NIPT is improved with high-depth resequencing.

Graphical abstract

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