Neurodevelopmental Disorder (Diagnosis)
Conditions
Keywords
Optical Genome Mapping, neurodevelopmental disorders, genome sequencing
Brief 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.
Interventions
GENETICOptical 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.
OTHERTrascriptome 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.
Sponsors
IRCCS Eugenio Medea
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Genotype-phenotype correlation | once at recruitment | Number of pathogenic structural variants found by OGM explaining the phenotype |
Countries
Italy
Contacts
Primary ContactMaria Clara Bonaglia PhD
Outcome results
None listed