Smelling a RAT: a reanalysis of suspected common aneuploidy results for the presence of rare autosomal trisomies (RATs) in non-invasive prenatal testing
Year: 2026
Type: article
Abstract: Introduction Rare autosomal trisomies (RATs) involve chromosomes other than 21, 18, 13 and XY and have come to prominence since the advent of non-invasive prenatal testing (NIPT). Occurring in ~1% of pregnancies, RATs can lead to pregnancy loss but usually appear in mosaic form and are confined to the placenta. Earlier versions of NIPT focused only on the common trisomies but some clinics subsequently expanded to all chromosomes to take account of RATs. This received some criticism as many detected RATs may not be clinically significant, possibly leading to unnecessary pregnancy anxiety. Of particular concern are ‘suspected aneuploidy’ calls, where the result shows evidence of aneuploidy by visual inspection but is not called by the analysis algorithm. Here, presence of a RAT could be skewing the algorithm, which was calibrated on the assumption that the RAT chromosomes were disomic.Methods In a study of 21 396 NIPT cases, 485 common (not RAT) aneuploidies and 110 ‘suspected aneuploidies’ 43 had follow-up information available by amniocentesis or live birth; 14 were ‘suspected aneuploidy’ with normal follow-up information. We tested the hypotheses that the discordance was due to a RAT disrupting the calling algorithm (discordance because of biological reasons) by rerunning the NIPT with a protocol capable of detecting RATs.Results All had full concordance with follow-up and outcome data. We thus reject the hypothesis that ‘suspected aneuploidies’ with discordant follow-up results were due to RATs.Conclusions Suspected aneuploidy results are, most likely, not the result of a RAT; we provide much-needed information to improve analysis algorithms in terms of calling thresholds, allowing increased sensitivity from paired-end sequencing results.
Source: BMJ connections.
Institutions: University of Kent, Oxford Fertility, University College London
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7223680034