Dataset Information

Clinical experience with single-nucleotide polymorphism-based non-invasive prenatal screening for 22q11.2 deletion syndrome.

ABSTRACT:

Objectives

To evaluate the performance of a single-nucleotide polymorphism (SNP)-based non-invasive prenatal test (NIPT) for the detection of fetal 22q11.2 deletion syndrome in clinical practice, assess clinical follow-up and review patient choices for women with high-risk results.

Methods

In this study, 21 948 samples were submitted for screening for 22q11.2 deletion syndrome using a SNP-based NIPT and subsequently evaluated. Follow-up was conducted for all cases with a high-risk result.

Results

Ninety-five cases were reported as high risk for fetal 22q11.2 deletion. Diagnostic testing results were available for 61 (64.2%) cases, which confirmed 11 (18.0%) true positives and identified 50 (82.0%) false positives, resulting in a positive predictive value (PPV) of 18.0%. Information regarding invasive testing was available for 84 (88.4%) high-risk cases: 57.1% (48/84) had invasive testing and 42.9% (36/84) did not. Ultrasound anomalies were present in 81.8% of true-positive and 18.0% of false-positive cases. Two additional cases were high risk for a maternal 22q11.2 deletion; one was confirmed by diagnostic testing and one had a positive family history. There were three pregnancy terminations related to screening results of 22q11.2 deletion, two of which were confirmed as true positive by invasive testing.

Conclusions

Clinical experience with this SNP-based non-invasive screening test for 22q11.2 deletion syndrome indicates that these deletions have a frequency of approximately 1 in 1000 in the referral population with most identifiable through this test. Use of this screening method requires the availability of counseling and other management resources for high-risk pregnancies.

SUBMITTER: Gross SJ

PROVIDER: S-EPMC5064640 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Publications

Clinical experience with single-nucleotide polymorphism-based non-invasive prenatal screening for 22q11.2 deletion syndrome.

Gross S J SJ Stosic M M McDonald-McGinn D M DM Bassett A S AS Norvez A A Dhamankar R R Kobara K K Kirkizlar E E Zimmermann B B Wayham N N Babiarz J E JE Ryan A A Jinnett K N KN Demko Z Z Benn P P

Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology 20160105 2

<h4>Objectives</h4>To evaluate the performance of a single-nucleotide polymorphism (SNP)-based non-invasive prenatal test (NIPT) for the detection of fetal 22q11.2 deletion syndrome in clinical practice, assess clinical follow-up and review patient choices for women with high-risk results.<h4>Methods</h4>In this study, 21 948 samples were submitted for screening for 22q11.2 deletion syndrome using a SNP-based NIPT and subsequently evaluated. Follow-up was conducted for all cases with a high-risk ...[more]

PMID: 26396068

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Project description:ObjectiveTo assess the performance of a non-invasive prenatal screening test (NIPT) for a panel of dominant single-gene disorders (SGD) with a combined population incidence of 1 in 600.MethodsCell-free fetal DNA isolated from maternal plasma samples accessioned from 14 April 2017 to 27 November 2019 was analyzed by next-generation sequencing, targeting 30 genes, to look for pathogenic or likely pathogenic variants implicated in 25 dominant conditions. The conditions included Noonan spectrum disorders, skeletal disorders, craniosynostosis syndromes, Cornelia de Lange syndrome, Alagille syndrome, tuberous sclerosis, epileptic encephalopathy, SYNGAP1-related intellectual disability, CHARGE syndrome, Sotos syndrome and Rett syndrome. NIPT-SGD was made available as a clinical service to women with a singleton pregnancy at ≥ 9 weeks' gestation, with testing on maternal and paternal genomic DNA to assist in interpretation. A minimum of 4.5% fetal fraction was required for test interpretation. Variants identified in the mother were deemed inconclusive with respect to fetal carrier status. Confirmatory prenatal or postnatal diagnostic testing was recommended for all screen-positive patients and follow-up information was requested. The screen-positive rates with respect to the clinical indication for testing were evaluated.ResultsA NIPT-SGD result was available for 2208 women, of which 125 (5.7%) were positive. Elevated test-positive rates were observed for referrals with a family history of a disorder on the panel (20/132 (15.2%)) or a primary indication of fetal long-bone abnormality (60/178 (33.7%)), fetal craniofacial abnormality (6/21 (28.6%)), fetal lymphatic abnormality (20/150 (13.3%)) or major fetal cardiac defect (4/31 (12.9%)). For paternal age ≥ 40 years as a sole risk factor, the test-positive rate was 2/912 (0.2%). Of the 125 positive cases, follow-up information was available for 67 (53.6%), with none classified as false-positive. No false-negative cases were identified.ConclusionsNIPT can assist in the early detection of a set of SGD, particularly when either abnormal ultrasound findings or a family history is present. Additional clinical studies are needed to evaluate the optimal design of the gene panel, define target populations and assess patient acceptability. NIPT-SGD offers a safe and early prenatal screening option. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Dataset Information

Clinical experience with single-nucleotide polymorphism-based non-invasive prenatal screening for 22q11.2 deletion syndrome.

Objectives

Methods

Results

Conclusions

Publications

Clinical experience with single-nucleotide polymorphism-based non-invasive prenatal screening for 22q11.2 deletion syndrome.

Similar Datasets

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