NCT06833489

Transcriptomic Analysis to Put an End to Misdiagnosis in Patients With Rare Muscle Diseases

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Assistance Publique Hopitaux De Marseille · Academic / Other
• Sex: All
• Age: —
• Healthy volunteers: Not accepted

Summary

Since 2017, more than 250 analyses performed at the Molecular Genetics Laboratory of the Timone Enfant Hospital have yielded negative results in patients with rare genetic muscle diseases. The researchers hypothesise that some of these misdiagnosed patients carry pathogenic RNA (transcript) disrupting variants that were not identified by DNA sequencing. In fact, DNA sequencing analyses can be negative despite the presence of a pathogenic variant that disrupts RNA splicing or expression, causing a genetic disease. For this reason, RNA sequencing can provide a diagnosis in patients who have not been diagnosed by DNA sequencing, thus putting an end to diagnostic wandering. Thus, as a descriptive prevalence study, the objectives are first to determine the rate of positive diagnoses made by the RNAseq approach in patients with muscle diseases that have not yet been diagnosed, and then to identify the genomic characteristics of the pathogenic variants identified in patients by RNAseq analysis, in order to facilitate the identification of this type of variant in future patients. 50 patients will be included in this study during 2 years.

Conditions

• Rare Genetic Muscle Diseases
• Muscular Dystrophy, Duchenne
• Muscular Dystrophy, Becker
• Congenital Myopathy
• Pompe Disease (Infantile-Onset)

Interventions

Type	Name	Description
OTHER	ARN extraction from muscle biopsies	There will be no visits from participants, so we will be using samples already in the Biological Resources Centre (CRB). RNA will be extracted from muscle biopsies taken as part of the treatment. RNAseq libraries will be sequenced by the Genomics and Bioinformatics Platform (GBiM) at Marseille Medical Genetics (MMG, U1251, AMU). Sequencing will be performed in paired-end (2\*100 bp) on Illumina's Novaseq 6000 system (50 million clusters per sample, 100 M paired-end reads) and then analysed by bioinformatics.

Timeline

• Start date: 2025-03-01
• Primary completion: 2026-09-01
• Completion: 2027-03-01
• First posted: 2025-02-18
• Last updated: 2025-02-18

Locations

1 site across 1 country: France