Purpose: Using genome-wide noninvasive prenatal screening (NIPS), we detected a 20-megabase specific deletion starting at 10q25 in eight pregnancies. The deletion could not be confirmed by invasive testing. Since all 10(q25→qter) deletions started close to the FRA10B fragile site in 10q25, we investigated whether the pregnant women were indeed carriers of FRA10B. Methods: We performed NIPS analysis for all autosomes using single-read sequencing. Analysis was done with the WISECONDOR algorithm. Culture of blood lymphocytes with bromodeoxyuridine was used to detect FRA10B expansions. Fluorescence in situ hybridization and array analysis were used to find maternal and/or fetal deletions. Results: We confirmed the presence of a FRA10B expansion in all four tested mothers. Fluorescence in situ hybridization and array analysis confirmed the presence of a maternal mosaic deletion of 10(q25→qter). Conclusion: The recurring 10(q25→qter) deletion detected with NIPS is a false-positive result caused by a maternal low-level mosaic deletion associated with FRA10B expansions. This has important consequences for clinical follow-up, as invasive procedures are unnecessary. Expanded maternal FRA10B repeats should be added to the growing group of variants in the maternal genome that may cause false-positive NIPS results.

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Keywords false-positive results, FRA10B, fragile sites, NIPS, noninvasive prenatal screening
Persistent URL dx.doi.org/10.1038/gim.2018.32, hdl.handle.net/1765/113015
Journal Genetics in Medicine
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Huijsdens–van Amsterdam, K. (Karin), Straver, R. (Roy), Maarle, M.C, Knegt, A.C, Van Opstal, A.R.M, Sleutels, F, … Sistermans, E.A. (2018). Mosaic maternal 10qter deletions are associated with FRA10B expansions and may cause false-positive noninvasive prenatal screening results. Genetics in Medicine, 20(11), 1472–1476. doi:10.1038/gim.2018.32