Using multi-omics to diagnose mitochondrial diseases

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

This study is testing a new way to diagnose mitochondrial diseases by looking closely at RNA from muscle and skin samples of patients who have had unclear genetic test results.

Quick facts

• Study type: Observational
• Enrollment: 66 (estimated)
• Sex: All
• Sponsor: Centre Hospitalier Universitaire de Nice (other)
• Locations: 9 sites (Nice, CHU de NICE and 8 other locations)
• Trial ID: NCT04920812 on ClinicalTrials.gov

What this trial studies

MITOMICS focuses on improving the diagnosis of mitochondrial diseases by analyzing RNA sequencing results from muscle and fibroblast samples. The study includes 66 patients suspected of mitochondrial myopathy who have previously undergone negative mitochondrial DNA and whole exome sequencing. By employing a novel computational approach that integrates multi-omics data, the study aims to identify which RNA-Seq results are most informative for interpreting variants of uncertain significance (VUS) found in genetic testing. This innovative methodology seeks to enhance diagnostic accuracy and identify specific molecular signatures associated with mitochondrial diseases.

Who should consider this trial

Good fit: Ideal candidates are patients suspected of mitochondrial diseases with muscular signs and negative mitochondrial DNA and whole exome sequencing results.

Not a fit: Patients with suspected mitochondrial diseases that do not involve muscle or those with identified causal variants will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more accurate diagnoses for patients with mitochondrial diseases, enabling better-targeted treatments.

How similar studies have performed: Previous studies have shown that combining whole exome sequencing with RNA sequencing can improve the diagnosis of mitochondrial diseases, indicating a promising approach.

Eligibility criteria

Inclusion Criteria:

* Patients suspected of a mitochondrial disease with muscular signs (clinical, histological or biochemical)
* Patients with negative mtDNA and WES NGS in trio
* Patients with routine muscle and skin biopsies available
* Blood samples from parents and / or relatives available for segregation studies
* Informed consent of the study signed by the patient or the legal representatives of the minor patient or under guardianship
* Patients affiliated to social security

Exclusion Criteria:

* Patients with suspected mitochondrial disease without muscle involvement
* Patients for whom the mtDNA NGS and WES have not been performed
* Patients with suspected mitochondrial disease with causal variant identified
* Refusal to sign the informed consent for the study
* Insufficient amount of frozen material or culture failure for fibroblasts

Where this trial is running

Nice, CHU de NICE and 8 other locations

• CHU de Nice — Nice, CHU de NICE, France (RECRUITING)
• C.H.R.U. Brest — Brest, France, France (NOT_YET_RECRUITING)
• Chu de Nantes — Nantes, France, France (RECRUITING)
• chu Angers — Angers, France (RECRUITING)
• Chu Brest — Brest, France (NOT_YET_RECRUITING)
• APHM — Marseille, France (RECRUITING)
• APHM — Marseille, France (RECRUITING)
• Chu Montpellier — Montpellier, France (RECRUITING)
• CHU Nantes — Nantes, France (NOT_YET_RECRUITING)

Study contacts

• Principal investigator: SYLVIE BANNWARTH — Centre Hospitalier Universitaire de Nice
• Study coordinator: SYLVIE BANNWARTH

Conditions: Mitochondrial Diseases