Neurodevelopmental Disorders
Conditions
Keywords
whole genome sequencing, transcriptome analysis, genotype phenotype, structural variants
Brief summary
to bridge the gap between the molecular structure of CNV and the effect on the phenotype, considering NDDs as complex diseases, as they are a consequence of the imbalance in several dosage-sensitive genes, we might try to approach them through different --omics investigations (genomics, epigenomics, transcriptomics) according to the emerging field of network medicine. This holistic can provide valuable insight into understanding peculiar molecular mechanisms and unsuspected molecular interactions that contribute to the pathogenesis of the condition and possibly pave the way for uncovering new drug strategies that even if they do not heal the patient may improve his performance and the social interaction
Interventions
DIAGNOSTIC_TESTWGS and transcriptome analysis
In light of the inconsistencies between the CNV and the phenotypic outcome, we expect that WGS analysis will reveal that part of these CNVs have a more complex structure than the one disentangled by CMA and FISH. We hypothesize that CNV should reflect a perturbed genome folding configuration at several hierarchical levels of chromatin organization, such as disruption of TADs boundaries. To investigate this aspect, we plan to examine expression profiles of immortalized lymphoblastoid B-cell lines (LBLs) derived from normal controls and patients. We expect to find a subset of down- or up-regulated genes located inside the rearranged region which in turn may alter the expression of other genes, possibly leading to perturbation of disease-related pathways
Sponsors
IRCCS Eugenio Medea
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
Patients with neurodevelopmental disorders carrying a genomic rearrangement identified through chromosomal microarray analysis (CMA)
Exclusion criteria
NA
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of likely pathogenic structural variants | once at recruitment | Number of likely pathogenic structural variants found by whole genome sequencing and transcriptome analysis. |
| Number of patients for whom a genotype-phenotype correlation is found | once at recruitment | Number of patients for whom a genotype-phenotype correlation is found based on results of whole genome sequencing and transcriptome analysis. |
Countries
Italy
Outcome results
None listed