Omic Approaches to Neurodevelopmental Disabilities

Omic Approaches to Characterize the Functional and Phenotypic Consequences of Rare Structural Genomic Variants in Neurodevelopmental Disabilities and Congenital Anomalies

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

Study Overview

• Status: Completed
• Conditions: Neurodevelopmental Disorders
• Intervention / Treatment: Diagnostic test: WGS and transcriptome analysis

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • LC
    • Bosisio Parini, LC, Italy, 23842
      • Scientific Institute IRCCS Eugenio Medea

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

NA

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Whole Genome Sequencing (WGS) and transcriptome analysis; 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; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: IRCCS Eugenio Medea

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2021
• Primary Completion (Actual): July 28, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: March 21, 2024
• First Submitted That Met QC Criteria: March 21, 2024
• First Posted (Actual): March 29, 2024

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 21, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: whole genome sequencing; transcriptome analysis; structural variants; genotype phenotype
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders
• Other Study ID Numbers: 1001 (Registro Nacional Estudios Clinicos (RNEC))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No