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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-A01079-38 | Other Identifier | RCB |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequencing of RNAseq libraries | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ARN extraction from muscle biopsies | Other | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| rate of positive diagnoses using the RNAseq approach | to determine the rate of positive diagnoses made using the RNAseq approach in patients with muscle diseases who have not yet been diagnosed. A patient is considered to be in diagnostic limbo if DNA sequencing of 200 genes responsible for muscle diseases has not identified pathogenic variants responsible for the patient's phenotype. Investigators are going to use transcriptomic analysis (RNA sequencing) in combination with innovative bioinformatics tools to identify variants with a deleterious effect at RNA level in patients with undiagnosed muscle diseases. This will make it possible to establish a molecular diagnosis and put an end to misdiagnosis in many patients. | From enrollment to the end of study at 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Identification of genomic characteristics | identify the genomic characteristics of pathogenic variants identified by the RNAseq approach. This analysis could potentially uncover certain characteristics that are specific to this type of variant, making it possible to suggest their presence in other undiagnosed patients in the future. | From enrollment to end of study at 24 months |
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Inclusion Criteria:
This criterion is necessary to limit the analysis to patients with muscular diseases among all the patients analysed by the Molecular Genetics Laboratory.
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Svetlana GOROKHOVA Dr | Contact | +33491381927 | promotion.interne@ap-hm.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hopital Timone | Recruiting | Marseille | 13005 | France |
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|
| ID | Term |
|---|---|
| D020388 | Muscular Dystrophy, Duchenne |
| D009224 | Myotonia Congenita |
| D006009 | Glycogen Storage Disease Type II |
| ID | Term |
|---|---|
| D009136 | Muscular Dystrophies |
| D020966 | Muscular Disorders, Atrophic |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
| D009468 | Neuromuscular Diseases |
| D009422 | Nervous System Diseases |
| D040181 | Genetic Diseases, X-Linked |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D020967 | Myotonic Disorders |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D020140 | Lysosomal Storage Diseases, Nervous System |
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D008661 | Metabolism, Inborn Errors |
| D006008 | Glycogen Storage Disease |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| D016464 | Lysosomal Storage Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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