NCT06851377

Expanding NGS Data with Optical Genome Mapping (OGM)

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

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: IRCCS Eugenio Medea · Academic / Other
• Sex: All
• Age: 2 Years
• Healthy volunteers: Not accepted

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)

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2024-05-23
• Primary completion: 2026-12-01
• Completion: 2026-12-01
• First posted: 2025-02-28
• Last updated: 2025-02-28

Locations

1 site across 1 country: Italy