Incidental detection of familial <i>APP</i> duplication: an unusual reason for a false positive NIPT result of trisomy 21

Meschino, Wendy S.; Miller, Kristen; Bedford, H. Melanie

doi:10.1002/pd.4783

Cited by 12 publications

(8 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of all reported false positive cases, 65 euploid cases (36%) had an NIPT positive for T21, 59 euploid cases (32%) were predicted to have T18, 47 cases (26%) were predicted to have T13, one case (0.5%) was predicted to have T22 and one (0.5%) T9 . One case (0.5%) had an NIPT result indicating monosomy 18 .…”

Section: Resultsmentioning

confidence: 99%

“…In one case (2%), the explanation was found in a T21 positive vanished twin, and in another case (2%), the mother turned out to have a supernumerary ring derived from chromosome 18 in 35% of her cells (maternal mosaicism) . One case (2%) was described with a maternal and fetal chromosome 21 duplication causing the false positive result . Nine cases (15%) were reported as false positive cases because of maternal cancer .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Discordant non-invasive prenatal testing (NIPT) - a systematic review

et al. 2017

View full text Add to dashboard Cite

With a high sensitivity and specificity, non-invasive prenatal testing (NIPT) is an incomparable screening test for fetal aneuploidy. However, the method is rather newly introduced, and experiences with discordant results are few. We did a systematic review of literature reporting details of false positive and false negative NIPT results. Discordant sex chromosome results were not included. We identified 22 studies reporting case details. In total, 206 discordant cases were included, of which 88% were false positive and 12% false negative. Details on maternal age, gestational age, platform/company, Z-score, fetal fraction, results and explanation were specified. The main reasons for discordant results were confined placental mosaicism, maternal copy number variation, vanished twin, maternal cancer and true fetal mosaicism. A very high percentage of cases (67%) were reported with no obvious biological or technical explanation for the discordant result. The included cases represent only a minor part of the true number of false positive or false negative NIPT cases identified in fetal medicine clinics around the world. To ensure knowledge exchange and transparency of NIPT between laboratories, we suggest a systematic recording of discordant NIPT results, as well as a quality assurance by external quality control and accreditation. © 2017 John Wiley & Sons, Ltd.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Discordant non-invasive prenatal testing (NIPT) - a systematic review

et al. 2017

View full text Add to dashboard Cite

show abstract

“…There are also other sources of false-positive results some of which may well be increased when the NIPT is expanded to include the full genome. This would include small partial maternal imbalances (5,38,39), rare maternal mosaicism such as trisomy 8 (40), maternal malignancy (40)(41)(42), aneuploid vanished twins (43), as well as the non-biological technical limitations of the testing. The estimate for the false-positive rate could therefore be substantially higher than 0.59%.…”

Section: Cytogenetically Recognizable Imbalancesmentioning

confidence: 99%

Expanding non‐invasive prenatal testing beyond chromosomes 21, 18, 13, X and Y

Benn

2016

Clinical Genetics

View full text Add to dashboard Cite

Non-invasive prenatal testing (NIPT) based on cell-free DNA in maternal plasma is being expanded to include additional chromosome abnormalities beyond those involving chromosomes 21, 18, 13, X and Y. Review of population cytogenetic data provides insight into the likely number of additional abnormalities detectable. Additional clinically significant and cytogenetically recognizable abnormalities are present in less than 0.1% of newborns but clinically significant, or potentially significant, sub-microscopic imbalances are expected to be present in 1.7%. Cytogenetic studies on chorionic villus samples suggests that after excluding abnormalities involving chromosomes 21, 18, 13, X and Y, approximately 0.6% of NIPT results may be positive for an unbalanced abnormality attributable to mosaicism but most of these will not be confirmed at amniocentesis or in newborns. NIPT has also been developed for specific microdeletion syndromes and initial experience is now available. Laboratory procedures such as deeper sequencing and additional data analytics are rapidly evolving but even with existing protocols, it is already clear that NIPT does not necessarily need to be limited to trisomies 21, 18, 13 and the sex-chromosome abnormalities. Patient educational materials and genetic counseling services need to be available for women offered expanded NIPT.

show abstract

“…41,42 This has the advantage of reducing false-positive trisomy calls due to benign CNVs that are present in only one part of the chromosome, 43 but has the disadvantage of identifying maternal, and in some cases, extended family CNVs. 44 Thus, there are different genetic counseling implications for a CNV detected by NIPS, in comparison with the other maternal medical conditions discussed in this review.…”

Section: Cnvsmentioning

confidence: 98%

“…Important factors to consider regarding the likelihood of a CNV resulting in a false-positive call include the size of the maternal CNV, whether the fetus inherits the CNV, the percent fetal fraction, the depth of sequencing, and the coefficient of variation of sequence reads for the chromosome of interest. 42,52 Finally, the numerous ethical and genetic counseling issues involved in incidental detection of maternal CNVs were illustrated in a case described by Meschino et al 44 NIPS was performed for two soft anatomic markers in the fetus; the results were positive for trisomy 21. The report had a commentary section, which mentioned the observation of a duplication outside the Down syndrome critical region at 21q22 that included APP.…”

Section: Cnvsmentioning

confidence: 99%

Cherchez la femme: maternal incidental findings can explain discordant prenatal cell-free DNA sequencing results

Bianchi

2018

Genetics in Medicine

View full text Add to dashboard Cite

Circulating DNA fragments in a pregnant woman's plasma derive from three sources: placenta, maternal bone marrow, and fetus. Prenatal sequencing to noninvasively screen for fetal chromosome abnormalities is performed on this mixed sample; results can therefore reflect the maternal as well as the fetoplacental DNA. Although it is recommended that pretest counseling include the possibility of detecting maternal genomic imbalance, this seldom occurs. Maternal abnormalities that can affect a prenatal screening test result include disorders that affect the size and metabolism of DNA, such as B12 deficiency, autoimmune disease, and intrahepatic cholestasis of pregnancy. Similarly, maternal tumors, both benign and malignant, can release DNA fragments that contain duplications or deletions. Bioinformatics algorithms can subsequently interpret the raw sequencing data incorrectly, resulting in false-positive test reports of fetal monosomies or test failures. Maternal sex-chromosome abnormalities, both constitutional and somatic, can generate results that are discordant with fetal ultrasound examination or karyotype. Maternal copy-number variants and mosaicism for autosomal aneuploidies can also skew interpretation. A maternal etiology should therefore be considered in the differential diagnosis of prenatal cell-free DNA test failures, false-positive and false-negative sequencing results. Further study is needed regarding the clinical utility of reporting maternal incidental findings.

show abstract

Incidental detection of familial APP duplication: an unusual reason for a false positive NIPT result of trisomy 21

Cited by 12 publications

References 10 publications

Discordant non-invasive prenatal testing (NIPT) - a systematic review

Discordant non-invasive prenatal testing (NIPT) - a systematic review

Expanding non‐invasive prenatal testing beyond chromosomes 21, 18, 13, X and Y

Cherchez la femme: maternal incidental findings can explain discordant prenatal cell-free DNA sequencing results

Contact Info

Product

Resources

About