Expanding NGS Data with Optical Genome Mapping (OGM)

NCT06851377 | Recruiting

• 1 other identifier: 1089
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Neurodevelopmental Disorder (Diagnosis)

Keywords

Optical Genome Mapping, neurodevelopmental disorders, genome sequencing

Outcome Measures

Primary Outcomes (1)

• Genotype-phenotype correlation

  Number of pathogenic structural variants found by OGM explaining the phenotype

  once at recruitment

Study Arms (1)

Expanding NGS data with Optical Genome Mapping (OGM)

EXPERIMENTAL

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); Other: Trascriptome analysis

Interventions

Optical Genome Mapping (OGM) and Whole Genome Sequencing (WGS) GENETIC

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.

Expanding NGS data with Optical Genome Mapping (OGM)

Trascriptome analysis OTHER

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.

Expanding NGS data with Optical Genome Mapping (OGM)

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• IRCCS Eugenio Medea: lead

Study Sites (1)

Cytogenetic Unit of Medical Genetic Laboratory

Bosisio Parini, Lecco, 23842, Italy

RECRUITING

MeSH Terms

Conditions

Neurodevelopmental Disorders; Disease

Interventions

Whole Genome Sequencing

Condition Hierarchy (Ancestors)

Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques

Central Study Contacts

Maria Clara Bonaglia PhD

CONTACT

+39 031 877913; mariaclara.bonaglia@lanostrafamiglia.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2025
• First Posted: February 28, 2025
• Study Start: May 23, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 28, 2025

Record last verified: 2025-02

Locations

IT (1)