Expanding NGS Data with Optical Genome Mapping (OGM)

IRCCS Eugenio Medea

Status: Enrolling

Conditions: Neurodevelopmental Disorder (Diagnosis)

Treatments: Genetic: Optical Genome Mapping (OGM) and Whole Genome Sequencing (WGS); Other: Trascriptome analysis

Study type: Interventional

Funder types: Other

Identifiers

NCT06851377

1089

Details and patient eligibility

About

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Expanding NGS data with Optical Genome Mapping (OGM)

Experimental group

Description:

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.

Treatment:

Other: Trascriptome analysis

Genetic: Optical Genome Mapping (OGM) and Whole Genome Sequencing (WGS)