ClinicalTrials.gov record NCT06475651
Characterization and Contribution of Genome-wide DNA Methylation (DNA Methylation Episignatures) in Rare Diseases With Prenatal Onset
Characterization and Contribution of Genome-wide DNA Methylation (DNA Methylation Episignatures) in Rare Diseases With Prenatal Onset
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This observational study analyzes genome-wide DNA methylation (episignatures) in fetal samples and in children's blood. It includes fetuses and children with selected rare genetic conditions (for example CHARGE and KABUKI syndromes) and matched negative controls. The study aims to define fetal reference episignatures and to compare fetal, postnatal, and amniotic-fluid methylation patterns.
What it is studying. Whether consistent genome-wide DNA methylation episignatures can be defined from fetal DNA (from amniotic fluid or frozen postmortem tissues) and whether those fetal episignatures differ from postnatal blood-based episignatures. The study also looks for episignatures associated with pathogenic variants in CHD7 and KMT2D and for new signatures linked to HYLS1, TCTN3, and FLVCR2.
What the researchers hope to learn. Scientific goals: to define fetal reference DNA methylation episignatures; to identify epigenetic signatures associated with CHD7 (CHARGE) and KMT2D (KABUKI); to compare fetal versus postnatal and tissue versus amniotic-fluid methylation patterns; to identify new fetal epigenetic signatures for HYLS1, TCTN3, and FLVCR2; and to measure statistical prediction parameters for each identified signature.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
It is necessary to define reference DNA Methylation Episignatures from fetal DNA. The hypotheses are:
- It is possible to define reference DNA Methylation Episignatures from fetal DNA extracted from amniotic fluid or frozen tissues collected during the postmortem examination
- Fetal DNA Methylation Episignatures may be different to postanal DNA Methylation Episignatures defined on DNA extracted from blood
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Genetic
- Methylation analysis
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
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
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
Congenital anomalies (CA) complicate 3 to 5% of pregnancies and may be associated with genetic disorders. Diagnosis of genetic diseases is a major medical challenge, especially during pregnancy. Over the past two decades, next-generation sequencing (NGS) has revolutionized our ability to identify the genetic condition associated with CA. During pregnancy, prenatal exome sequencing identified an additional diagnosis in around 30% of fetuses with CA when standard chromosomal investigations (karyotype and chromosomal microarray analysis, CMA) fail to provide a diagnosis. Despite these major advances, around 40% of rare diseases remain unsolved, including 10-15% of patients harboring variants of uncertain significance (VUS). After birth, additional functional analyses ("multi-OMICS"), including genome-wide DNA methylation studies, may be offered to reclassify VUS. DNA methylation anomalies play an important role in pathologies (developmental disorders and oncology). DNA methylation Episignatures, defined as the cumulative DNA methylation patterns occurring at multiple CpG dinucleotides across the genome, have been recognized to be intricately associated with many human traits, including age, sex, and disease status. Recently, DNA Methylation Episignatures have been identified in the blood of children or adults for several well-characterized genetic diseases. However, these postnatal DNA Methylation Episignatures cannot be used during pregnancy, because DNA methylation changes from one tissue to another and during time, especially during fetal developpement. In addition, the tissues available during pregnancy are different from those analyzed postnatally (blood).
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Researchers will use existing stored DNA from amniotic fluid, fetal tissue (lung), or whole blood for genome‑wide DNA methylation analysis (methylation arrays) and will use associated clinical data. No new invasive procedures are described in the registry; participation centers on allowing reuse of samples and data. Parents/guardians must give the required consent or non‑objection for reuse, or (for deceased fetuses) have previously signed consent and have no recorded opposition.
How the study is structured. Cross-sectional observational study. Researchers analyze DNA from fetal tissue, amniotic fluid, and children's blood using genome-wide methylation analysis (EPIC array) to compare affected cases and matched negative controls.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- This is an observational study, so the study itself gives no treatment. What would taking part involve for me, and would it change my usual care?
- The listed sites are in France. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Kabuki syndrome
Important dates
- Study start
- Feb 26, 2026
- Primary completion
- Aug 26, 2026 (estimated)
- Study completion
- Aug 26, 2026 (estimated)
- Target enrollment
- 63 participants (estimated)
- Last updated on registry
- Mar 27, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Nicolas BOURGON, MD, PhD 📞 +33 1 42 19 27 96 ✉ nicolas.bourgon@aphp.fr
- Nelly BRIAND, PhD 📞 0144381862 ✉ nelly.briand@aphp.fr
Participating sites (1)
- Department of Genomic Medicine for Rare Diseases and the Multidisciplinary Center for Prenatal Diagnosis of the Necker-Enfants malades HospitalRecruiting
Paris, 75015 · France
- Nicolas BOURGON, MD, PhD · : +33 1 42 19 27 96 · nicolas.bourgon@aphp.fr
Terms used on this page · explanations by MedicalUpdates.ai
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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