Optical genome mapping to find genetic causes of multiple congenital anomalies with or without intellectual disability
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
This project will try optical genome mapping to detect structural genetic changes in people with multiple congenital anomalies (with or without intellectual disability) when prior whole-genome sequencing did not give an answer.
Quick facts
| Phase | Not applicable |
|---|---|
| Study type | Interventional |
| Enrollment | 55 (estimated) |
| Sex | All |
| Sponsor | University Hospital, Clermont-Ferrand Academic / other |
| Locations | 1 site (Clermont-Ferrand) |
| Trial ID | NCT07370792 on ClinicalTrials.gov |
What this trial studies
Patients who have at least two congenital anomalies and a non-contributive short-read whole-genome sequencing result will be invited to provide blood for optical genome mapping and related cytogenetic work-up. Samples will be pseudonymized, processed for long-fragment DNA extraction and, when available, cultured lymphocytes to obtain chromosomal pellets for comparison. The laboratory will search for structural variants and other genomic rearrangements that short-read sequencing or microarray may have missed. Findings will be compared with prior genetic results to determine whether optical genome mapping yields additional diagnostic information.
Who should consider this trial
Good fit: People with at least two congenital anomalies (with or without intellectual disability), weighing more than 5 kg, who have had non-contributive whole-genome sequencing and can give informed consent (or whose guardians can).
Not a fit: Patients with a previously identified non-genetic cause (infectious, environmental, or toxic), those unable to provide a usable blood sample, or those whose condition is due to single-nucleotide changes already identified are unlikely to benefit.
Why it matters
Potential benefit: If successful, this could provide a genetic diagnosis for patients who remain unexplained after standard testing, ending part of the diagnostic odyssey and informing care and family planning.
How similar studies have performed: Previous reports indicate optical genome mapping can detect structural variants missed by short-read genomic methods, but its added diagnostic yield in this specific population is still being defined.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Clermont-Ferrand
- CHU clermont-Ferrand — Clermont-Ferrand, France (Recruiting)
Study contacts
- Study coordinator: Lise Laclautre
- Email: promo_interne_drci@chu-clermontferrand.fr
- Phone: +33473754963
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.