Expanding NGS Data with Optical Genome Mapping (OGM)

ConditionNeurodevelopmental Disorder (Diagnosis)

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age2+

SponsorIRCCS Eugenio Medea

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

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.
Trascriptome analysis
Other intervention
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.

Treatment groups

60 Participants

are divided into 1 treatment group

Group A: Expanding NGS data with Optical Genome Mapping (OGM)Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

Genotype-phenotype correlation

Number of pathogenic structural variants found by OGM explaining the phenotype

Time frame

once at recruitment

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

IRCCS Eugenio Medea

Lead sponsor

Source ClinicalTrials.gov

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