Contribution of Optical Genome Mapping (OGM) in the Diagnosis of Multiple Congenital Malformations With or Without Intellectual Disability Without Genetic Abnormality (CARTOGEN-N)

January 20, 2026 updated by: Céline PEBREL-RICHARD

CARTOGEN-N_Contribution of Optical Genome Mapping (OGM) in the Diagnosis of Multiple Congenital Malformations With or Without Intellectual Disability Without Genetic Abnormality Detected by Whole Genome Sequencing

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 Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

  1. × 5 mL heparinized blood tube

    Patient 12-20 kg:

  2. × 5 mL EDTA blood tubes

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
55

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  • Patients presenting with at least two congenital anomalies, with or without intellectual disability, and weighing more than 5 kg.
  • Whole-genome sequencing performed by the AURAGEN laboratory deemed non-contributive (absence of class 4 or 5 variants, or identification of a VUS, or identification of only one variant in the context of a recessive disorder).
  • Patient covered by a social security scheme.
  • Patient able to understand and to oppose participation in the study.
  • Written informed consent for genetic analyses, signed either by the patient or by their legal representatives (for minors), after clear and fair information about the study has been provided.

Non-Inclusion Criteria

  • Patients for whom a non-genetic cause (infectious, environmental, or toxic) has been previously identified.
  • Inability to obtain a compliant sample.
  • Patient or holder of parental authority under guardianship or legal protection, deprived of liberty, or placed under court-ordered protection.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Diagnostic
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: single arm of patients with congenital malformations
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
diagnostic yield of optical genome mapping (OGM) in multiple congenital anomalies with or without intellectual disability when whole-genome sequencing (WGS) is non-contributive
Time Frame: day 1 (inclusion and blood collection)
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).
day 1 (inclusion and blood collection)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of reclassified variants intially considered as VUS (Variants of Uncertain/Unknown Signification)
Time Frame: day 1 (inclusion and blood collection)
Assessment of the number of variants initially classified as VUS (variants of uncertain/unknown significance) that were reclassified as benign or pathogenic variants
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)
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
Time Frame: day 1 (inclusion and blood collection)
Evaluation of technical duration (hours)
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
Time Frame: day 1 (inclusion and blood collection)
failure rate number
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
Time Frame: day 1 (inclusion and blood collection)
reprocessing rate number
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
Time Frame: day 1 (inclusion and blood collection)
Evaluation of biological interpretation time (hours)
day 1 (inclusion and blood collection)
Assess the impact of using these new technologies on patient management.
Time Frame: day 1 (inclusion and blood collection)
Percentage of patients for whom the OGM results led to a change in clinical management.
day 1 (inclusion and blood collection)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Céline PEBREL-RICHARD

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Lise Laclautre, University Hospital, Clermont-Ferrand

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 18, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 9, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 20, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 27, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 27, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 20, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AOI 2024 PEBREL-RICHARD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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