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

What this Trial Is About

Researchers are investigating a new approach to improve genetic diagnosis in patients with suspected mitochondrial diseases who remain undiagnosed after standard genetic testing. The study focuses on analyzing RNA transcripts to better understand variants of uncertain significance (VSI) that may affect gene expression or RNA splicing, which are often missed or hard to interpret through current genetic methods. This research aims to compare RNA analysis from blood cells and fibroblast tissue to help resolve these diagnostic challenges. The study involves collecting RNA samples from both skin fibroblast biopsies and blood samples of 10 patients previously identified with VSI in candidate genes related to mitochondrial disease. Researchers will use high-throughput RNA sequencing (RNA-Seq) to analyze transcript data from both sources, focusing on genes linked to the patients' symptoms. This method aims to save time and reduce costs by providing a uniform diagnostic strategy compared to more time-consuming targeted tests. Participants will undergo a skin biopsy and blood sample collection during the inclusion visit. Researchers will evaluate whether RNA from blood cells provides equivalent diagnostic information to fibroblast RNA. The study will measure outcomes including diagnostic yield and the ability to analyze RNA-Seq data over 17 months. The goal is to establish a more accessible and efficient diagnostic tool for mitochondrial diseases and potentially expand its use in clinical practice.

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