Expanding NGS Data with Optical Genome Mapping (OGM) (OGM)

February 24, 2025 updated by: IRCCS Eugenio Medea

Expanding NGS Data with Optical Genome Mapping (OGM): More Comprehensive Variant Detection in Children with Unexplained Rare Genetic Disorders

Over 50% of pediatric neurological and neurodevelopmental disorders lack a molecular diagnosis after standard DNA sequencing and molecular karyotyping. This is due to technical limitations, incomplete variant interpretation, and inadequate genotype-phenotype correlations. New sequencing technologies are crucial for clinical decision-making, offering complete profiles of variants in a patient's DNA to personalize treatment. Optical Genome Mapping (OGM) can detect nearly all structural variants in one experiment. This project aims to use OGM alongside NGS to improve diagnostic yield in 60 children with severe disorders who tested negative for NGS/CMA.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • 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 Locations

  • Italy
    • Lecco
      • Bosisio Parini, Lecco, Italy, 23842
        • Recruiting
        • Cytogenetic Unit of Medical Genetic Laboratory
        • Contact:
          • Maria C Bonaglia, Master Degree
          • Phone Number: +39 031877913

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

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • individuals without a molecular diagnosis (negative to ES/CMA analyses);
  • individuals with genetic diagnoses that explain only one component of their primary phenotype;
  • individuals carrying one or more variants of uncertain clinical significance
  • individuals with a phenotype highly reminiscent of clinically and molecularly well-defined syndromes (i.e., Marfan Syndrome) but negative to routine molecular analysis.

Exclusion Criteria:

  • individuals who have not undergone initial diagnostic genetic tests (ES/CMA)

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
Intervention / Treatment
Experimental: Expanding NGS data with Optical Genome Mapping (OGM)
OGM will be used alongside WGS to improve diagnostics in 60 children with severe NDDs lacking a molecular diagnosis after initial CMA and exome analyses.
Genetic: Optical Genome Mapping (OGM) and Whole Genome Sequencing (WGS)
After identifying causal SVs via OGM, WGS will determine rearrangement breakpoints and examine nearby genes within 100 kb that may have altered expression due to positional effects.
Other: Trascriptome analysis
Following genomic characterization results, transcriptome analysis will be performed on patient-derived lymphoblastoid B-cell lines or fibroblasts to investigate the molecular implications of candidate SVs found in the OGM analysis and identify potential transcriptome abnormalities, such as splicing variants, in patients with atypical clinical features.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Genotype-phenotype correlation
Time Frame: once at recruitment
Number of pathogenic structural variants found by OGM explaining the phenotype
once at recruitment

Collaborators and Investigators

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

Sponsor

IRCCS Eugenio Medea

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)

May 23, 2024

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2026

Study Registration Dates

First Submitted

February 24, 2025

First Submitted That Met QC Criteria

February 24, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

February 24, 2025

Last Verified

February 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1089

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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