NCT06762678: ATOMICS

Transcriptomic Approach for the Identification and Prioritization of Genome Variants in Neurodevelopmental Disorders With Malformation

Not yet recruiting NA Last updated 7 January 2025

What this trial tests

NA trial testing RNA sequencing and whole genome sequencing in a trio way in Neurodevelopmental Disorders and Developmental Abnormalities in 58 participants. Not yet recruiting.

Timeline

1 February 2025

Primary endpoint
1 August 2026

1 August 2027

Quick facts

Lead sponsor	University Hospital, Angers
Phase	NA
Status	Not yet recruiting
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	diagnostic
Enrollment	58
Start date	1 February 2025
Primary completion	1 August 2026
Estimated completion	1 August 2027

Drugs / interventions tested

• RNA sequencing and whole genome sequencing in a trio way

Conditions studied

• Neurodevelopmental Disorders and Developmental Abnormalities — all drugs for Neurodevelopmental Disorders and Developmental Abnormalities →

Sponsor

University Hospital, Angers

Who can join

Eligibility, any sex, with Neurodevelopmental Disorders and Developmental Abnormalities. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Three million persons in France are impacted by rare diseases. Amid the 7000 different diseases which are identified today, neurodevelopmental disorders are the main symptoms found interesting 35 000 birth every years, according to the French Health Authority. In half of these cases, patients are under 5 years old and a molecular diagnosis is only available in 50% of them, associated with a diagnostic wandering exceeding 5 years for 25% of every patients.

High throughput DNA sequencing technologies are powerful tools to elucidate new causative variants. Although the diagnostic yield was refined by DNA-seq, data interpretation and technology limits remain the two major obstacles which still need be overcame. Missing a molecular diagnosis through a genomic approach alone highlight the need to integrate multi-omic approaches such as Ribonucleic Acid sequencing. This sequencing level allows new insight such like the evidence of aberrant gene expression, mono allelic allele expression, or abnormal alternative splicing. It makes possible too, to detect variants which are unable to be found via genome sequencing only.

Recently, a diagnostic performance improvement has been described trough the association of the two technics, i.e. Ribonucleic Acid-seq and genome sequencing, in a context of neuromuscular diseases. However, only few studies were carry out on neurodevelopmental disorders in addition with malformative features. We demonstrated by the end of 2022, a diagnostic results enhancement by carrying genome sequencing plus Ribonucleic Acid-seq at the same time on patient with previously exome negative analysis. Moreover in 2023, Dekker et al. work shed light on a diagnostic yield improvement via the same analytic schema.

In face of those first observations, our study aims to evaluate the diagnostic contribution of Ribonucleic Acid-seq paired with genome sequencing in a trio way versus the genome sequencing in a solo way, to identify the find a final diagnosis for patient presenting neurodevelopmental disorders with developmental abnormalities and without an evident diagnosis after chromosome microarray and/or exome sequencing analysis.

To successfully carry out our study, we plan to recruit patient in a protocol considered with minimal risk and minimal constraints, to compare Ribonucleic Acid-seq performed on fibroblasts, in addition to genome sequencing in a solo or a trio manner, to trio genome sequencing alone, with the final objective in mind to obtain an etiology diagnostic for a patient presenting with neurodevelopmental disorders and development abnormalities.

Publications & conference data

No peer-reviewed publications indexed yet for this trial.