OC06.01: Single cell sequencing of circulating extravillous trophoblasts for non‐invasive fetal copy number variant screening
Year: 2024
Type: conference-abstract
Abstract: Pathogenic microdeletions/duplications (pCNVs) account for a significant perinatal morbidity/mortality and have a 1/100-200 prevalence in the general prenatal population. Cell-free DNA non-invasive testing (cfNIPT) shows significant limitations for comprehensive profiling of pCNVs <7Mb in size. A proof-of-concept study demonstrated the feasibility of a novel cell-based NIPT (cbNIPT) for circulating extravillous trophoblasts (cEVTs) isolation and single cell sequencing for fetal CNV detection down to ~800kb. The scope of the study is to demonstrate cbNIPT scientific validity in a large blinded prospective performance study comparing the fetal genomic result with that of cEVTs screening. 1388 high-risk pregnancies were enrolled to obtain a statistically significant pCNV/aneuploidies number. Blood was collected from pregnant women at 11-22+6 wg before invasive diagnostic procedure and processed with proprietary laboratory workflow not optimised for recovery rate. 1070 had CMA ± karyotype and the remainders with karyotype only. Screen positive rate for aneuploidies and pCNV was 18.9% and 11.2%, respectively. Totally 203 pCNVs ≥ 1Mb were detected and 84.2% of them (171/203) were 1-7 Mb in size. Of note, pCNVs < 1 Mb were also detected. Examples of pCNV are: 22q11.2del (7 spanning 600Kb-3Mb), 22q11dup (1 of 3Mb), 2q37del (2 of 2.1Mb and 3.9Mb), 8q24.3del (2 of 600kb), 7q22.3del (1 of 800Kb), 1q21.1del (1 of 800kb), Wolf-Hirschhorn Sy (1 of 2.9Mb) and 1 Williams Beuren Sy (1 of 1Mb). At the time of submission, the clinical database was locked and confirmatory clinical data analysis was ongoing. Analysis of cEVTs from maternal blood offers the detection of genome wide pCNV < 1 Mb, below the resolution of cell-free DNA screening. In the general pregnancy population, this would allow the opportunity for a significant reduction of residual risk for pCNV at early gestational weeks. CbNIPT clinical performance data will be provided together with an estimated rate of detection compared to cfNIPT.
DOI: 10.1002/uog.27754
Authors: F. Grati, T. Stampalija, E. Bertucci, C. Izzi, P. Volpe, I. Fabietti, A. Novelli, L. Pasquini, S. Ornaghi, E. Bevilacqua, D. Paladini, T. Ghi, D. Lattuada, C. Fregona, A. Sponzilli, M. Signorelli, G. Rembouskos, L. Caforio, P. Bagolan, F. Restaldi, F. Petraglia, A. Locatelli, D. Pasquetti, N. Volpe, C. Amadesi, R. Foti, I. Molinaro, E. Giovannone, E. Signore, M. Iannitiello, L. Monasta, G. Buson, C. Bolognesi, C. Forcato, A. Doffini, T.J. Musci, E. Ferrazzi
Institutions: Menarini Silicon Biosystems (Italy), University of Trieste, IRCCS Materno Infantile Burlo Garofolo, University of Modena and Reggio Emilia, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, University of Brescia, Bambino Gesù Children's Hospital, Azienda Ospedaliero-Universitaria Careggi, Azienda Ospedaliera San Gerardo, University of Milano-Bicocca, Agostino Gemelli University Polyclinic, Istituto Giannina Gaslini, University of Parma, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Florence, Università Cattolica del Sacro Cuore
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W4402359364