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Parallel Sequencing of Fetal Genome and RNA in the Presence of Ultrasound Warning Signs: a Complementary Approach for the Prenatal Diagnosis of Rare Diseases.

NCT07790536 · Status: NOT_YET_RECRUITING · Type: OBSERVATIONAL · Enrollment: 100

Last updated 2026-08-27

No results posted yet for this study

Summary

Prenatal exome sequencing (ES) is increasingly used for fetuses with ultrasound-detected anomalies but yields 10-15% variants of uncertain significance (VUS), limiting diagnostic performance, particularly in prenatal settings with incomplete phenotypes.

This study aims to evaluate the added value of combined prenatal genome sequencing (GS) and RNA sequencing (RNA-Seq), which are not currently part of routine care. Conducted at AP-HP, it will compare the diagnostic yield of GS + RNA-Seq with the current standard approach (chromosomal microarray analysis + ES), according to variant type (coding, non-coding, and structural). The contribution of systematic RNA-Seq to rapid VUS resolution will be specifically assessed.

Overall, this project will assess the feasibility, diagnostic performance, and clinical utility of implementing GS + RNA-Seq in prenatal diagnosis, supporting future integration into routine care in France.

Conditions

  • Couples Eligible for Prenatal Exome Sequencing

Interventions

DIAGNOSTIC_TEST

Genome Sequencing (GS) + RNA-Sequencing (RNA-Seq)

Couples whose indication for trio exome sequencing is approved by a multidisciplinary prenatal diagnostic center are enrolled during a pre-test genetic consultation, during which written informed consent is obtained from both partners. As part of routine care, fetal samples are collected by amniocentesis and parental blood samples are obtained for chromosomal microarray analysis (CMA) and trio exome sequencing (ES), analyzed locally. Amniotic fluid cell cultures are systematically prepared and stored. For research purposes, portions of fetal and parental samples are processed at Pitié-Salpêtrière and sequenced at SeqOIA for trio genome sequencing (GS). Bioinformatics analysis is performed using the MOABI platform, with interpretation via the Gleaves-P interface. RNA sequencing (RNA-Seq) is performed on RNA extracted from amniotic fluid cell cultures at Necker Hospital. For couples included at Necker only, maternal plasma DNA is also sequenced. Non-invasive GS results are for rese

Sponsors & Collaborators

  • URC-CIC Paris Descartes Necker Cochin

    collaborator OTHER

  • Imagine

    collaborator UNKNOWN

  • Laboratoire SeqOIA

    collaborator UNKNOWN

  • MOABI

    collaborator UNKNOWN

  • Assistance Publique - Hôpitaux de Paris

    lead OTHER

Principal Investigators

  • Lucile BOUTAUD, Pharm.D PhD · Hôpital Necker Enfants Malades AP-HP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2026-09-30
Primary Completion
2028-03-31
Completion
2028-03-31

Countries

  • France

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07790536 on ClinicalTrials.gov