NCT06475651

Characterization and Contribution of Genome-wide DNA Methylation (DNA Methylation Episignatures) in Rare Diseases With Prenatal Onset

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 63 (estimated)
• Sponsor: Assistance Publique - Hôpitaux de Paris · Academic / Other
• Sex: All
• Age: 0 Years – 18 Years
• Healthy volunteers: Accepted

Summary

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

Detailed description

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).

Conditions

• Rare Fetal Genetic Diseases
• Congenital Malformation

Interventions

Type	Name	Description
GENETIC	Methylation analysis	Genomic DNA will be treated with bisulfite. 500 ng of processed DNA is then hybrized on an EPICv2 array Infinium methylation (Illumina, San Diego, CA, USA). This microarray enables the analysis of approximately 865 000 methylation sites at promoters, enhancers, CpG islands, intergenic and intragenic regions. It is the most widely used chip in the literature, including almost all of the EPIGENETIC SIGNATURES reported in human pathology.

Timeline

• Start date: 2026-02-26
• Primary completion: 2026-08-26
• Completion: 2026-08-26
• First posted: 2024-06-26
• Last updated: 2026-03-27

Locations

1 site across 1 country: France