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Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies

Atypical fetal chromosomal anomalies are more frequent than previously recognized and can affect fetal development. We propose a screening strategy for a genome-wide non-invasive prenatal test (NIPT) to detect these atypical chromosomal anomalies (ACAs). Two sample cohorts were tested. Assay perform...

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Autores principales: Kleinfinger, Pascale, Lohmann, Laurence, Luscan, Armelle, Trost, Detlef, Bidat, Laurent, Debarge, Véronique, Castaigne, Vanina, Senat, Marie-Victoire, Brechard, Marie-Pierre, Guilbaud, Lucie, Le Guyader, Gwenaël, Satre, Véronique, Laurichesse Delmas, Hélène, Lallaoui, Hakima, Manca-Pellissier, Marie-Christine, Boughalem, Aicha, Valduga, Mylene, Hodeib, Farah, Benachi, Alexandra, Costa, Jean Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464024/
https://www.ncbi.nlm.nih.gov/pubmed/32752152
http://dx.doi.org/10.3390/jcm9082466
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author Kleinfinger, Pascale
Lohmann, Laurence
Luscan, Armelle
Trost, Detlef
Bidat, Laurent
Debarge, Véronique
Castaigne, Vanina
Senat, Marie-Victoire
Brechard, Marie-Pierre
Guilbaud, Lucie
Le Guyader, Gwenaël
Satre, Véronique
Laurichesse Delmas, Hélène
Lallaoui, Hakima
Manca-Pellissier, Marie-Christine
Boughalem, Aicha
Valduga, Mylene
Hodeib, Farah
Benachi, Alexandra
Costa, Jean Marc
author_facet Kleinfinger, Pascale
Lohmann, Laurence
Luscan, Armelle
Trost, Detlef
Bidat, Laurent
Debarge, Véronique
Castaigne, Vanina
Senat, Marie-Victoire
Brechard, Marie-Pierre
Guilbaud, Lucie
Le Guyader, Gwenaël
Satre, Véronique
Laurichesse Delmas, Hélène
Lallaoui, Hakima
Manca-Pellissier, Marie-Christine
Boughalem, Aicha
Valduga, Mylene
Hodeib, Farah
Benachi, Alexandra
Costa, Jean Marc
author_sort Kleinfinger, Pascale
collection PubMed
description Atypical fetal chromosomal anomalies are more frequent than previously recognized and can affect fetal development. We propose a screening strategy for a genome-wide non-invasive prenatal test (NIPT) to detect these atypical chromosomal anomalies (ACAs). Two sample cohorts were tested. Assay performances were determined using Cohort A, which consisted of 192 biobanked plasma samples—42 with ACAs, and 150 without. The rate of additional invasive diagnostic procedures was determined using Cohort B, which consisted of 3097 pregnant women referred for routine NIPT. Of the 192 samples in Cohort A, there were four initial test failures and six discordant calls; overall sensitivity was 88.1% (37/42; CI 75.00–94.81) and specificity was 99.3% (145/146; CI 96.22–99.88). In Cohort B, there were 90 first-pass failures (2.9%). The rate of positive results indicating an anomaly was 1.2% (36/3007) and 0.57% (17/3007) when limited to significant unbalanced chromosomal anomalies and trisomies 8, 9, 12, 14, 15, 16, and 22. These results show that genome-wide NIPT can screen for ACAs with an acceptable sensitivity and a small increase in invasive testing, particularly for women with increased risk following maternal serum screening and by limiting screening to structural anomalies and the most clinically meaningful trisomies.
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spelling pubmed-74640242020-09-04 Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies Kleinfinger, Pascale Lohmann, Laurence Luscan, Armelle Trost, Detlef Bidat, Laurent Debarge, Véronique Castaigne, Vanina Senat, Marie-Victoire Brechard, Marie-Pierre Guilbaud, Lucie Le Guyader, Gwenaël Satre, Véronique Laurichesse Delmas, Hélène Lallaoui, Hakima Manca-Pellissier, Marie-Christine Boughalem, Aicha Valduga, Mylene Hodeib, Farah Benachi, Alexandra Costa, Jean Marc J Clin Med Article Atypical fetal chromosomal anomalies are more frequent than previously recognized and can affect fetal development. We propose a screening strategy for a genome-wide non-invasive prenatal test (NIPT) to detect these atypical chromosomal anomalies (ACAs). Two sample cohorts were tested. Assay performances were determined using Cohort A, which consisted of 192 biobanked plasma samples—42 with ACAs, and 150 without. The rate of additional invasive diagnostic procedures was determined using Cohort B, which consisted of 3097 pregnant women referred for routine NIPT. Of the 192 samples in Cohort A, there were four initial test failures and six discordant calls; overall sensitivity was 88.1% (37/42; CI 75.00–94.81) and specificity was 99.3% (145/146; CI 96.22–99.88). In Cohort B, there were 90 first-pass failures (2.9%). The rate of positive results indicating an anomaly was 1.2% (36/3007) and 0.57% (17/3007) when limited to significant unbalanced chromosomal anomalies and trisomies 8, 9, 12, 14, 15, 16, and 22. These results show that genome-wide NIPT can screen for ACAs with an acceptable sensitivity and a small increase in invasive testing, particularly for women with increased risk following maternal serum screening and by limiting screening to structural anomalies and the most clinically meaningful trisomies. MDPI 2020-08-01 /pmc/articles/PMC7464024/ /pubmed/32752152 http://dx.doi.org/10.3390/jcm9082466 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kleinfinger, Pascale
Lohmann, Laurence
Luscan, Armelle
Trost, Detlef
Bidat, Laurent
Debarge, Véronique
Castaigne, Vanina
Senat, Marie-Victoire
Brechard, Marie-Pierre
Guilbaud, Lucie
Le Guyader, Gwenaël
Satre, Véronique
Laurichesse Delmas, Hélène
Lallaoui, Hakima
Manca-Pellissier, Marie-Christine
Boughalem, Aicha
Valduga, Mylene
Hodeib, Farah
Benachi, Alexandra
Costa, Jean Marc
Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies
title Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies
title_full Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies
title_fullStr Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies
title_full_unstemmed Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies
title_short Strategy for Use of Genome-Wide Non-Invasive Prenatal Testing for Rare Autosomal Aneuploidies and Unbalanced Structural Chromosomal Anomalies
title_sort strategy for use of genome-wide non-invasive prenatal testing for rare autosomal aneuploidies and unbalanced structural chromosomal anomalies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464024/
https://www.ncbi.nlm.nih.gov/pubmed/32752152
http://dx.doi.org/10.3390/jcm9082466
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