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
IRCCS Eugenio Medea
60 participants
May 23, 2024
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria4
- 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 Criteria1
- individuals who have not undergone initial diagnostic genetic tests (ES/CMA)
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Interventions
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.
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.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT06851377