Clinical experience with a single‐nucleotide polymorphism‐based non‐invasive prenatal test for five clinically significant microdeletions. Issue 2 (17th November 2017)

• Record Type: Journal Article
• Authors: Martin, K.; Iyengar, S.; Kalyan, A.; Lan, C.; Simon, A.L.; Stosic, M.; Kobara, K.; Ravi, H.; Truong, T.; Ryan, A.; Demko, Z.P.; Benn, P.
• Is Part Of: Clinical genetics. Volume 93:Issue 2(2018)
• Page Start: 293
• Page End: 300
• Publication Date: 2017-11-17
• Subjects: aneuploidy -- microdeletion -- non‐invasive prenatal testing -- single‐nucleotide polymorphism -- submicroscopic chromosome abnormality; Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.13098
• Languages: English
• ISSNs: 0009-9163

Abstract

Abstract : Single‐nucleotide polymorphism (SNP)‐based non‐invasive 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 1‐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 4 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 (FPR) for 22q11.2 deletion syndrome decreased to 0.07% with the revised protocol. Similarly, the FPR for the other 4 disorders combined decreased from 0.56% to 0.07%. Minimal prevalences were estimated to be 1 in 1255 for 22q11.2 deletion syndrome and 1 in 1464 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. Abstract :