Combating the Diagnostic Impasse in Mitochondrial Diseases: a Transcriptomic Approach in Fibroblasts and Blood Cells

Launched by CENTRE HOSPITALIER UNIVERSITAIRE DE NICE · Sep 27, 2024

Keywords

ClinConnect Summary

This clinical trial is focused on improving the diagnosis of mitochondrial diseases, which are conditions that affect how our cells produce energy. Even with advanced genetic testing techniques, about half of the patients still do not receive a clear diagnosis. Researchers believe that some genetic variations can confuse test results, making it hard to determine their significance. To address this, the study will use a new approach called RNA sequencing (RNA-Seq) to analyze genetic material from both skin cells (fibroblasts) and blood cells of patients who have uncertain genetic findings. By comparing these two types of samples, the researchers hope to identify specific changes that could help clarify the diagnosis for these patients.

To be eligible for the trial, participants must be individuals suspected of having a mitochondrial disease and must have a specific type of genetic variation that is considered “possibly harmful.” This includes both children and adults, and consent will be needed from parents or guardians for minors. Participants will undergo a blood test and a skin biopsy, but the study aims to make the process as quick and less invasive as possible. The goal is to enhance understanding of these genetic variations, ultimately helping patients get a clearer diagnosis and better care.

Gender

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Eligibility criteria

• Inclusion Criteria:
• • General criteria: major or minor patients, sporadic or isolated cases
• * Pathology-related criteria :
• • Patients with suspected mitochondrial disease according to Morava criteria
• * Identification of a predicted VSI, "possibly pathogenic" by SPICE and/or SpliceAI biοstatistical and biοinfοrmatic prediction tools, in a gene :
• • Compatible with the patient's phenotype
• • With sufficient expression in blood (TPM\>1, GTEX) predicted as "possibly pathogenic" by SPICE and/or SpliceAI biοstatistical and biοinfοrmatic prediction tools.
• • Signature of informed consent, for minor patients signature of at least one of the 2 parents or the representative of parental authority
• Exclusion Criteria:
• • Patient whose identified VSI is in the same gene as a patient already included in the study;
• • Persons deprived of liberty by judicial or administrative decision;
• • Persons hospitalized without consent;
• • Persons of full age or minors under legal protection or unable to express their consent;
• • Inability of the subject to cooperate.