An interventional study of blood sample in Congenital Malformations, sponsored by Céline PEBREL-RICHARD. Recruiting at 1 site in France. Per ClinicalTrials.gov, last updated 2026-11-04.
Sponsored by Céline PEBREL-RICHARD · Not applicable, Interventional, and Diagnostic
Congenital malformations result from an embryonic or foetal developmental disorder (DD) affecting one or more systems (cardiac, skeletal, nervous, etc.). These are referred to as multiple congenital anomalies (MCAs). They may be associated with an intellectual disability (ID)1.
Chromosomal analysis on Chromosomal Microarray Analysis (CMA) and gene panels or exome sequencing are the respective gold standard methods for chromosomal and molecular diagnosis of DD respectively2. In cases where no diagnosis is established after these first-line tests, short-read whole genome sequencing (WGS), via the Plan France Medicine Genomic 2020-2025 (AURAGEN), may be considered. This approach allows for diagnosis in nearly 40% of patients with DD3,4. However, many patients remain in diagnostic deadlock, likely due to the technical limitations of these methods, which potentially be overcome by emerging methodologies such as optical genome mapping (OGM)5,6,7,8,9. The investigators propose to systematically perform OGM in 30 patients presenting with MCA+/-ID who have inconclusive WGS result10.
The main objective is to assess the contribution of OGM in identifying structural variants not detected or poorly characterised by WGS in this clinical context. This work will also contribute to the ongoing of OGM in routine diagnostics and determine its role in the overall genetic diagnosis of MCA+/-ID. Additionally it may lead to the identification of new candidate genes and/or mechanisms of pathogenicity. If the results are promising, further clinical could expand this preliminary work into a larger-scale project. Improving the genetic diagnosis of DD should enhance the medical management of patients, currently in diagnostic deadlock, and their families.
Study Workflow
Pre-analytical Phase
Participation in the study will be offered to all patients meeting the inclusion and non-inclusion criteria by an investigator from the Department of Genetics, during a medical consultation in which the non-contributive whole-genome sequencing (WGS) result will have been communicated (Figure 1). Information regarding the study procedures and objectives will be provided at that time. The information sheet and consent form will be given to the patient (if an adult) or to the holders of parental authority (if the patient is a minor). After obtaining consent for both the genetic investigations and participation in the research project, the patient may be enrolled in the study. Blood samples required for the study will be collected, transferred to the laboratory, and secured for analysis according to the following protocol:
Patient > 20 kg:
2 × 5 mL EDTA blood tubes
× 5 mL heparinized blood tube
Patient 12-20 kg:
Patient 5-12 kg:
1 × 5 mL EDTA blood tube
Samples will be sent to the Cytogenetics Department, where they will be pseudonymized and secured. At least three aliquots of 1.5 mL EDTA blood and the remaining volume will be frozen at -80 °C for DNA extraction and long-fragment DNA extraction. A cell culture (peripheral blood lymphocytes) will also be performed to obtain a fixed chromosomal pellet from the heparinized tube, when available. If the heparinized sample is not available and the results of optical genome mapping require confirmation of a chromosomal abnormality by karyotype or FISH (i.e., contributive result), a second blood draw will be proposed during the clinical results-return consultation.
Analysis Frozen samples from the Cytogenetics Department of Clermont-Ferrand University Hospital (one per patient) will be transferred via TSE to the Department of Genetics at Reims University Hospital, designated to perform optical genome mapping while awaiting installation of the Saphyr scanner at Clermont-Ferrand University Hospital (DAN 2025 application).
Extraction, labeling, and imaging of long DNA molecules will be performed using the manufacturer's kits, following the provided instructions.
Results and Interpretation
Raw data will be analyzed and validated by cytogeneticists at Reims University Hospital using Bionano Access and Solve® software. Data will also be securely shared with the project lead, responsible for:
Performing a second independent analysis (with Bionano Access and Solve, available in the Cytogenetics Department), leveraging expertise acquired through participation in previous projects.
Providing final interpretation of results and disseminating clinically relevant findings for patient management.
Each sample will therefore benefit from dual review and dual expertise, ensuring the reliability of the results.
Parental segregation studies may be proposed to facilitate biological interpretation. If needed, collection of parental samples and consent procedures will be coordinated by the Department of Medical Genetics at Clermont-Ferrand University Hospital. Conclusive results will be communicated to the clinician who prescribed the WGS for patient management and genetic counselling.
781 studies on the registry are indexed under Congenital Abnormalities; 77 are open to participants now.
This study's planned enrollment of 55 is above the median of 40 across 466 interventional studies indexed under Congenital Abnormalities.
Browse Congenital Abnormalities studies →This is the only study on the registry with Céline PEBREL-RICHARD as lead sponsor.
Compared within Congenital Abnormalities, the registry's first condition term, which may not be this study's main condition. Counted across the registry records on this site, refreshed daily. How we classify →
Inclusion Criteria
Non-Inclusion Criteria
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Genetic: blood sample
A blood sample will be collected after obtaining consent from the patient and/or their legal guardians. The number of tubes required (1 to 3) will be determined according to the patient's weight, for the purpose of performing optical genome mapping and any necessary confirmatory analyses in the event that a structural variant is identified.
diagnostic yield of optical genome mapping (OGM) in multiple congenital anomalies with or without intellectual disability when whole-genome sequencing (WGS) is non-contributive
Assessing the diagnostic yield of optical genome mapping (OGM) in multiple congenital anomalies with or without intellectual disability when whole-genome sequencing (WGS) is non-contributive (absence of causal genetic variation or detection of a variant of uncertain significance (VUS) or a single variant in a recessive disorder).
Time frame: day 1 (inclusion and blood collection)
Number of reclassified variants intially considered as VUS (Variants of Uncertain/Unknown Signification)
Assessment of the number of variants initially classified as VUS (variants of uncertain/unknown significance) that were reclassified as benign or pathogenic variants
Time frame: day 1 (inclusion and blood collection)
Number of patients in whom a new candidate gene/pathogenic mechanism is identified
Time frame: day 1 (inclusion and blood collection)
Evaluation of the feasibility (duration) of the technique in current practice in 1st-line, 2nd-line (after routine tests such as chromosomal microarray, exome sequencing…), or 3rd-line in the case of non-contributive WGS based on several criteria
Evaluation of technical duration (hours)
Time frame: day 1 (inclusion and blood collection)
Evaluation of the feasibility of the technique (failure) in current practice in 1st-line, 2nd-line (after routine tests such as chromosomal microarray, exome sequencing…), or 3rd-line in the case of non-contributive WGS based on several criteria
failure rate number
Time frame: day 1 (inclusion and blood collection)
Evaluation of the feasibility of the technique (reprocessing) in current practice in 1st-line, 2nd-line (after routine tests such as chromosomal microarray, exome sequencing…), or 3rd-line in the case of non-contributive WGS based on several criteria
reprocessing rate number
Time frame: day 1 (inclusion and blood collection)
Evaluation of the feasibility of the technique (interpretation) in current practice in 1st-line, 2nd-line (after routine tests such as chromosomal microarray, exome sequencing…), or 3rd-line in the case of non-contributive WGS based on several criteria
Evaluation of biological interpretation time (hours)
Time frame: day 1 (inclusion and blood collection)
Assess the impact of using these new technologies on patient management.
Percentage of patients for whom the OGM results led to a change in clinical management.
Time frame: day 1 (inclusion and blood collection)
Plan to share: No
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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