Targeted capture enrichment followed by NGS: development and validation of a single comprehensive NIPT for chromosomal aneuploidies, microdeletion syndromes and monogenic diseases
Posted on 2019-11-22 - 05:59
Abstract Background Non-invasive prenatal testing (NIPT) has been widely adopted for the detection of fetal aneuploidies and microdeletion syndromes, nevertheless, limited clinical utilization has been reported for the non-invasive prenatal screening of monogenic diseases. In this study, we present the development and validation of a single comprehensive NIPT for prenatal screening of chromosomal aneuploidies, microdeletions and 50 autosomal recessive disorders associated with severe or moderate clinical phenotype. Results We employed a targeted capture enrichment technology powered by custom TArget Capture Sequences (TACS) and multi-engine bioinformatics analysis pipeline to develop and validate a novel NIPT test. This test was validated using 2033 cell-fee DNA (cfDNA) samples from maternal plasma of pregnant women referred for NIPT and paternal genomic DNA. Additionally, 200 amniotic fluid and CVS samples were used for validation purposes. All NIPT samples were correctly classified exhibiting 100% sensitivity (CI 89.7–100%) and 100% specificity (CI 99.8–100%) for chromosomal aneuploidies and microdeletions. Furthermore, 613 targeted causative mutations, of which 87 were unique, corresponding to 21 monogenic diseases, were identified. For the validation of the assay for prenatal diagnosis purposes, all aneuploidies, microdeletions and point mutations were correctly detected in all 200 amniotic fluid and CVS samples. Conclusions We present a NIPT for aneuploidies, microdeletions, and monogenic disorders. To our knowledge this is the first time that such a comprehensive NIPT is available for clinical implementation.
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Koumbaris, George; Achilleos, Achilleas; Nicolaou, Michalis; Loizides, Charalambos; Tsangaras, Kyriakos; Kypri, Elena; et al. (2019). Targeted capture enrichment followed by NGS: development and validation of a single comprehensive NIPT for chromosomal aneuploidies, microdeletion syndromes and monogenic diseases. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4750028.v1
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AUTHORS (16)
GK
George Koumbaris
AA
Achilleas Achilleos
MN
Michalis Nicolaou
CL
Charalambos Loizides
KT
Kyriakos Tsangaras
EK
Elena Kypri
PM
Petros Mina
CS
Carolina Sismani
VV
Voula Velissariou
GC
Georgia Christopoulou
PC
Pantelis Constantoulakis
EM
Emmanouil Manolakos
IP
Ioannis Papoulidis
DS
Danai Stambouli
MI
Marios Ioannides
PP
Philippos Patsalis