The influence of SNP-based chromosomal microarray and NIPT on the diagnostic yield in 10,000 fetuses with and without fetal ultrasound anomalies

Srebniak, Malgorzata I.; Knapen, Maarten F. C. M.; Polak, Marike; Joosten, Marieke; Diderich, Karin E. M.; Govaerts, L.; Boter, Marjan; Kromosoeto, Joan N.R.; Hassel, Daniella A.C.M. van; Huijbregts, Gido; IJcken, Wilfred F. J. van; Heydanus, R.; Dijkman, A.; Toolenaar, Toon; Vries, Femke A.T. de; Knijnenburg, Jeroen; Go, Attie T.J.I.; Galjaard, Robert-Jan H; Opstal, Diane Van

doi:10.1002/humu.23232

Cited by 33 publications

(39 citation statements)

References 39 publications

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“…Grati et al (2017) reported that the following risks of finding a mosaicism in CVS after a positive cfDNA result: 2% for T21, 4% for T18 and 22% for T13. While cfDNA testing is highly sensitive and specific, false positive results can occur and therefore positive results should be confirmed with invasive testing .…”

Section: Chromosomal Abnormalitiesmentioning

confidence: 99%

Genetic syndromes associated with isolated fetal growth restriction

2020

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Early onset fetal growth restriction (FGR) may be due to impaired placentation, environmental or toxic exposure, congenital infections or genetic abnormalities. Remarkable research, mainly based on retrospective series, has been published on the diverse genetic causes. Those have become more and more relevant with the improvement in the accuracy of the analysis techniques and the rising of breakthrough genomewide methods such as the whole genome sequencing. However, no publication has presented an integrated view of management of those fetuses with an early and severe affection. In this review, we explored to which extent genetic syndromes can cause FGR fetuses without structural defects. The most common chromosomal abnormalities (Triploidies and Trisomy 18), submicroscopic chromosomal anomalies (22q11.2 microduplication syndrome) and single gene disorders (often associated with mild ultrasound findings) related to early and severe FGR had been analysed. Finally, we addressed the impact of epigenetic marks on fetal growth, a matter of growing importance. At the end of this review, we should be able to provide an adequate counseling to parents in terms of diagnosis, prognosis and management of those pregnancies.

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Section: Chromosomal Abnormalitiesmentioning

confidence: 99%

Genetic syndromes associated with isolated fetal growth restriction

2020

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“…The most common incidental findings were X-Linked Ichtyosis (OMIM #308100; 13 cases, six females and seven males), Hereditary Neuropathy with liability to Pressure Palsies (OMIM #162500; six cases), and Charcot-Marie-Tooth type 1A (OMIM #118200; five cases) (Table 1 and Table S3).Susceptibility CNVs were diagnosed in 1.6% (210/13 266) of our population; based on our national guidelines (see Vanakker et al and Section 4), one third of those (71/210 or 33.8%; 0.5% of the total population) were reported(Table S1). In cases with an ultrasound anomaly, 0.7% carried a reported susceptibility CNV; this was not significantly different compared with the prevalence in the entire prenatal population, in accordance with the fact that susceptibility CNVs are rarely associated with ultrasound anomalies.Table 1shows the most frequent susceptibility CNVs: the 22q11.2 duplication syndrome (OMIM #608363; 24 cases) and the 15q11.2 BP1-BP2 duplication17 (32 cases) are respectively the most common reported and unreported susceptibility CNV. Susceptibility CNVs were all cryptic.The overall added diagnostic value of using CMA compared with karyotyping was 1.8%.…”

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confidence: 99%

“…In the case of ultrasound anomalies, we observed a 4% difference (18.1% vs 22.1%) in the diagnostic yield of NIPT versus CMA (Table 2), clearly demonstrating that NIPT cannot replace CMA for this indication. With respect to the implementation of NIPT for pregnancies without ultrasound anomalies, concerns have also been raised, as subchromosomal pathogenic CNVs will be missed 32,33. In our population, 26.2% (83/317) of reported CNVs below 10 Mb were found in cases with the indication "an aberrant Down syndrome screening test," "advanced maternal age," or "other indications," all of which would have remained undetected with NIPT as the first-tier test, even when assuming a resolution similar to that of karyotyping.…”

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confidence: 99%

The Belgian MicroArray Prenatal (BEMAPRE) database: A systematic nationwide repository of fetal genomic aberrations

et al. 2018

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Objective With the replacement of karyotyping by chromosomal microarray (CMA) in invasive prenatal diagnosis, new challenges have arisen. By building a national database, we standardize the classification and reporting of prenatally detected copy number variants (CNVs) across Belgian genetic centers. This database, which will link genetic and ultrasound findings with postnatal development, forms a unique resource to investigate the pathogenicity of variants of uncertain significance and to refine the phenotypic spectrum of pathogenic and susceptibility CNVs. Methods The Belgian MicroArray Prenatal (BEMAPRE) consortium is a collaboration of all genetic centers in Belgium. We collected data from all invasive prenatal procedures performed between May 2013 and July 2016. Results In this three‐year period, 13 266 prenatal CMAs were performed. By national agreement, a limited number of susceptibility CNVs and no variants of uncertain significance were reported. Added values for using CMA versus conventional karyotyping were 1.8% in the general invasive population and 2.7% in cases with an ultrasound anomaly. Of the reported CNVs, 31.5% would have remained undetected with non‐invasive prenatal test as the first‐tier test. Conclusion The establishment of a national database for prenatal CNV data allows for a uniform reporting policy and the investigation of the prenatal and postnatal genotype–phenotype correlation.

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“…Future prospective studies will be needed to test in larger sample size, and prior to or in parallel with current NGS-or microarray-based PGS testing in order to better estimate the test performance statistics (23). Nonetheless, in the evolution of methods to better assess chromosomal copy number in the preimplantation embryo, from FISH to microarray and NGS (24)(25)(26), nanopore-based sequencing has the potential to offer rapid testing results within an IVF lab setting.…”

Section: Discussionmentioning

confidence: 99%

Rapid preimplantation genetic screening (PGS) using a handheld, nanopore-based, DNA sequencer

Wei

Weiss²,

Gaur³

et al. 2018

Preprint

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Objective: To determine if a handheld, nanopore-based DNA sequencer can be used for rapid preimplantation genetic screening (PGS).Design: Retrospective study.Setting: Academic medical center. Patient(s):Amplified genomic DNA from euploid and aneuploid trophectoderm biopsy samples (n=9) that was also tested using traditional next generation sequencing (NGS). Intervention(s):Short-read DNA library preparation and nanopore-based sequencing using a hand-held MinION sequencer. Main outcome measure(s):Comparison of cytogenetic testing result from NGS and nanoporebased sequencing and the time required for library preparation and sequencing. Result(s):Multiplexed short-read DNA library preparation was completed in 45 minutes.Sequencing times varied from 1 to 2 hours. These times compare favorably with NGS library preparation (>3.5 hours) and sequencing (>12 hours) times. Whole-chromosome aneuploidy screening results obtained from nanopore-based sequencing were identical to those obtained using NGS. Conclusion(s): Methods for PGS of embryos have evolved from FISH to microarrays and mostrecently to NGS. Here we report the first application of nanopore-based sequencing for PGS on trophecoderm biopsy samples using a rapid multiplex short-read nanopore sequencing library preparation. Aneuploidy screening could be performed on 5 samples in one nanopore flowcell with 1 to 2 hour sequencing times. Overall, nanopore sequencing is a promising tool to perform rapid PGS assay onsite with a rapid turnover time, enabling same day testing and embryo All rights reserved. No reuse allowed without permission.was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/274563 doi: bioRxiv preprint first posted online Mar. 1, 2018; 4 transfer thus obviating the need for complex, large and expensive DNA sequencers or frozen embryos.

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The influence of SNP-based chromosomal microarray and NIPT on the diagnostic yield in 10,000 fetuses with and without fetal ultrasound anomalies

Cited by 33 publications

References 39 publications

Genetic syndromes associated with isolated fetal growth restriction

Genetic syndromes associated with isolated fetal growth restriction

The Belgian MicroArray Prenatal (BEMAPRE) database: A systematic nationwide repository of fetal genomic aberrations

Rapid preimplantation genetic screening (PGS) using a handheld, nanopore-based, DNA sequencer

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