MITOMICS : a Multi-OMICS Approach for the Diagnosis of Mitochondrial Diseases (MITOMICS)
Interest of Multi-omics (WES / RNA-Seq) Approach to Fight Against the Diagnostic Deadlock in Mitochondrial Diseases
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: SYLVIE BANNWARTH
- Phone Number: 0492034702
- Email: bannwarth.s@chu-nice.fr
Study Locations
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Angers, France
- Recruiting
- CHU Angers
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Contact:
- Vincent PROCACCIO, MD
-
Brest, France
- Not yet recruiting
- CHU Brest
-
Contact:
- Pascale Marcorelles, Professor
-
Brest, France
- Not yet recruiting
- C.H.R.U. Brest
-
Contact:
- Jean Noury, MD
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Marseille, France
- Recruiting
- APHM
-
Contact:
- Shahram ATTARIAN, Professor
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Montpellier, France
- Recruiting
- CHU Montpellier
-
Contact:
- Cecilia MARELLI, Doctor
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Nantes, France
- Recruiting
- CHU de Nantes
-
Contact:
- Sandra Mercier, MD
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Nantes, France
- Not yet recruiting
- CHU Nantes
-
Contact:
- Yann PEREON, Professor
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Chu de Nice
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Nice, Chu de Nice, France, 06003
- Recruiting
- CHU de Nice
-
Contact:
- Phone Number: 0492034702
- Email: bannwarth.s@chu-nice.fr
-
Contact:
- Sylvie BANNWARTH, Professor
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Sampling Method
Study Population
Description
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
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Other
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
Mitochondrial diseases
annalysing with 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.
|
• Determination of the presence of specific molecular signatures at the RNA level in muscles and fibroblasts from patients
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
number of variations interpreted as responsible for the Mitochondrial diseases
Time Frame: baseline
|
• Comparison of the number of variations (splicing variant, expression level) or VUS, identified in WES, interpreted as responsible for the disease (class 4 or 5 variants) thanks to the RNA-Seq carried out at from a muscle biopsy or RNA-Seq performed from fibroblasts
|
baseline
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
RNA in mitochondiral deseases
Time Frame: baseline
|
Patients for whom the RNA-Seq could not be performed and reason for failure
|
baseline
|
|
variation of RNA in mitochondiral deseases
Time Frame: baseline
|
Variations identified by RNA-Seq, allowing interpretation of WES data (splicing aberrants, monoallelic expressions, etc.)
|
baseline
|
|
specific molecular signatures of mitochondiral deseases
Time Frame: baseline
|
Determination of the presence of specific molecular signatures at the RNA level in muscles and fibroblasts from patients
|
baseline
|
Collaborators and Investigators
Investigators
- Principal Investigator: SYLVIE BANNWARTH, Centre Hospitalier Universitaire de Nice
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 19-API-01
- 2020-A02651-38 (Registry Identifier: IDRCB)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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