Omic Approaches to Neurodevelopmental Disabilities

NCT06337396 | Completed

• 1 other identifier: 1001
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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

Conditions

Neurodevelopmental Disorders

Keywords

whole genome sequencing; transcriptome analysis; genotype phenotype; structural variants

Outcome Measures

Primary Outcomes (2)

• Number of likely pathogenic structural variants

  Number of likely pathogenic structural variants found by whole genome sequencing and transcriptome analysis.

  once at recruitment

• Number of patients for whom a genotype-phenotype correlation is found

  Number of patients for whom a genotype-phenotype correlation is found based on results of whole genome sequencing and transcriptome analysis.

  once at recruitment

Study Arms (1)

Whole Genome Sequencing (WGS) and transcriptome analysis

EXPERIMENTAL

to investigate by WGS analysis the genome of selected patients with a detailed clinical characterization. WGS will be also performed on the DNA of the parent from which originated the CNV to look for any potential genomic signatures predisposing to the rearrangement detected in his/her son/daughter. to investigate the expression profiles of structural variants by transcriptome analysis

Diagnostic Test: WGS and transcriptome analysis

Interventions

WGS and transcriptome analysis DIAGNOSTIC_TEST

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

Whole Genome Sequencing (WGS) and transcriptome analysis

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with neurodevelopmental disorders carrying a genomic rearrangement identified through chromosomal microarray analysis (CMA)

Sponsors & Collaborators

• IRCCS Eugenio Medea: lead

Study Sites (1)

Scientific Institute IRCCS Eugenio Medea

Bosisio Parini, LC, 23842, Italy

Location

MeSH Terms

Conditions

Neurodevelopmental Disorders

Interventions

Transcriptome

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Transcription, Genetic; Biochemical Phenomena; Chemical Phenomena; Gene Expression; Genetic Phenomena; Genetic Structures

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2024
• First Posted: March 29, 2024
• Study Start: May 5, 2021
• Primary Completion: July 28, 2023
• Study Completion: December 31, 2023
• Last Updated: March 29, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)