NCT04920812

MITOMICS : a Multi-OMICS Approach for the Diagnosis of Mitochondrial Diseases

Interest of Multi-omics (WES / RNA-Seq) Approach to Fight Against the Diagnostic Deadlock in Mitochondrial Diseases

• Status: Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 66 (estimated)
• Sponsor: Centre Hospitalier Universitaire de Nice · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

MITOMICS aims to determine which RNA-Seq results (from muscle or fibroblasts) are the most informative for the interpretation of VUS identified by WES for patients suspected of mitochondrial myopathy. Analysis of RNA-Seq and WES results will performed with a computational approach using an autoencoder-based method

Detailed description

Mitochondrial diseases (MD) are rare, clinically and genetically extremely heterogeneous, caused by a deficit of energy production via the mitochondria. Mitochondria are dependent on 2 genomes mitochondrial DNA and nuclear DNA, and many pathogenic variants carried by these 2 genomes are responsible for mitochondrial diseases. The diagnostic strategies for MD patients have evolved significantly with the emergence of Next Generation Sequencing (NGS) also accelerating the identification of the responsible gene. However, the diagnostic yield remains limited and requires the development of new approaches. Previous studies showed that WES and RNA-Seq combination improves the diagnosis of MD, essentially by helping in the interpretation of identified VUS. With MITOMICS project, we will included 66 patients suspected of a mitochondrial myopathy (clinical, histological or biochemical), with a negative mtDNA and WES NGS in trio. For each patient we will sequenced RNA from muscle and fibroblasts. Using a new innovative methology of multi-OMICS integration we will determined which RNA-Seq data (from muscle or fibroblasts) are the most informative for the interpretation of VUS identified by WES for patients suspected of mitochondrial myopathy. The results obtained will allow the interpretation of VUS and the identification of specific molecular signatures.

Conditions

• Mitochondrial Diseases

Interventions

Type	Name	Description
GENETIC	diagnosis of mitochondrial myopathy	• Determination of the presence of specific molecular signatures at the RNA level in muscles and fibroblasts from patients

Timeline

• Start date: 2022-03-07
• Primary completion: 2022-03-07
• Completion: 2025-09-07
• First posted: 2021-06-10
• Last updated: 2025-02-25

Locations

9 sites across 1 country: France