Expanding NGS Data with Optical Genome Mapping (OGM)
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Optical Genome Mapping (OGM) and Whole Genome Sequencing (WGS), Trascriptome analysis.
- Who it may be relevant to
- Registry conditions: Neurodevelopmental Disorder (Diagnosis). Basic parameters: from 2 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Italy
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Expanding NGS Data with Optical Genome Mapping (OGM): More Comprehensive Variant Detection in Children with Unexplained Rare Genetic Disorders
Overview
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.
Interventions
- 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.
Primary outcome measures
- Genotype-phenotype correlation [Time frame: once at recruitment]
Eligibility criteria
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)
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Diagnostic
Study locations
Italy · 1 center
- Cytogenetic Unit of Medical Genetic Laboratory — Bosisio Parini
Identifiers
NCT: NCT06851377 · 1089