Characterizing fetal DNA methylation patterns in prenatal genetic and congenital conditions
Characterization and Contribution of Genome-wide DNA Methylation (DNA Methylation Episignatures) in Rare Diseases With Prenatal Onset
This project tests whether unique genome-wide DNA methylation patterns in fetal samples can help diagnose rare prenatal genetic and congenital conditions.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 63 (estimated) |
| Ages | 0 Years to 18 Years |
| Sex | All |
| Sponsor | Assistance Publique - Hôpitaux de Paris Academic / other |
| Locations | 1 site (Paris) |
| Trial ID | NCT06475651 on ClinicalTrials.gov |
What this trial studies
This observational project will map genome-wide DNA methylation patterns (episignatures) from fetal DNA obtained from amniotic fluid and frozen postmortem tissues and compare them with postnatal blood-derived patterns. Participants include fetuses or children with pathogenic or likely pathogenic variants in genes such as CHD7, KMT2D, HYLS1, TCTN3, or FLVCR2, together with negative controls. Genome-wide methylation analysis will be used to define reference fetal episignatures and to test whether fetal signatures differ from those defined after birth. The study aims to create fetal-specific methylation references that could improve interpretation of prenatal genetic findings.
Who should consider this trial
Good fit: Ideal candidates are fetuses with available DNA from amniotic fluid or frozen postmortem tissues, or children with available blood DNA, who carry pathogenic or likely pathogenic variants in target genes (CHD7, KMT2D, HYLS1, TCTN3, FLVCR2) and whose parents consent to molecular testing and research.
Not a fit: Patients without available fetal or postmortem tissue or without relevant gene variants, and those whose conditions are not associated with methylation changes, are unlikely to benefit from this approach.
Why it matters
Potential benefit: If successful, this could increase diagnostic clarity for prenatal genetic disorders and help reclassify uncertain genetic variants, improving counseling and care decisions.
How similar studies have performed: Postnatal DNA methylation episignatures have been identified for several genetic disorders and helped reclassify variants, but defining fetal-specific episignatures for prenatal use is novel and not yet established.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Patient Inclusion Criteria: * Fetuses with a postmortem examination as part of the etiological diagnosis of developmental abnormality within the Genomic Medicine of Rare Diseases department of the Necker Children's Hospital, and whose DNA extracted from lung and amniotic fluid is available * OR a child cared for in the Genomic Medicine for Rare Diseases department of the Necker Children's Hospital, and whose DNA extracted from whole blood is available * with pathogenic or probably pathogenic variation in a gene following CHD7, KMT2D, HYLS1, TCTN3 or FLVCR2 * whose parents have consented to molecular genetic testing as part of diagnosis and research * Negative Controls : * Fetuses with a postmortem examination as part of the etiological diagnosis of developmental abnormality within the Genomic Medicine of Rare Diseases department of the Necker Children's Hospital, and whose DNA extracted from lung and amniotic fluid are available * OR a child cared for in the Genomic Medicine for Rare Diseases department of the Necker Children's Hospital, and whose DNA extracted from whole blood is available * does not have pathogenic or probably pathogenic variation in a gene following CHD7, KMT2D, HYLS1, TCTN3 or FLVCR2 * whose parents have consented to molecular genetic testing as part of diagnosis and research * For everyone: • For living participants: Non-objection by holders of parental authority to the reuse of clinical data and biological samples collected and stored in the context of care (consent of care). • For deceased participants: * Consent of the holders of parental authority to the use of the samples kept for research purposes, signed as part of the treatment * No mention of opposition to the reuse of clinical data from the treatment in the patient's medical record Exclusion Criteria: * Refusal of postmortem examination in case of fetal loss * Parents' refusal of molecular investigations
Where this trial is running
Paris
- Department of Genomic Medicine for Rare Diseases and the Multidisciplinary Center for Prenatal Diagnosis of the Necker-Enfants malades Hospital — Paris, France (Recruiting)
Study contacts
- Study coordinator: Nicolas BOURGON, MD, PhD
- Email: nicolas.bourgon@aphp.fr
- Phone: +33 1 42 19 27 96
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.