An interventional study of Blood collection and skin biopsy in Rare Genetic Disease, sponsored by Assistance Publique Hopitaux De Marseille. Recruiting at 1 site in France. Open to participants aged 0 Years to 99 Years. Per ClinicalTrials.gov, last updated 2026-05-08.
Sponsored by Assistance Publique Hopitaux De Marseille · Not applicable, Interventional, and Diagnostic
This study aims to answer a key question in the field of rare genetic diseases by determining the prevalence of deleterious variants at RNA level in undiagnosed patients with intellectual disability and/or neonatal hypotonia. This study will put an end to diagnostic erraticism in a number of patients.
Finally, the results of this study will make it possible to compare the two types of tissue used for RNAseq, with a view to facilitating the implementation of this analysis method in the diagnostic setting.
Rationale:
The majority of patients with intellectual disability or neonatal hypotonia remain undiagnosed, despite extensive genetic testing. In fact, standard analyses aimed at detecting abnormalities in the patient's DNA only enable a diagnosis to be made in a third of cases. Our hypothesis is that a certain number of these misdiagnosed patients carry anomalies (pathogenic variants) disrupting the RNA (transcript), which were not identified by DNA sequencing.
This study aims to answer a key question in the field of rare genetic diseases by determining the prevalence of deleterious variants at RNA level in undiagnosed patients with intellectual disability and/or neonatal hypotonia. This study will put an end to diagnostic erraticism in a number of patients.
Finally, the results of this study will make it possible to compare the two types of tissue used for RNAseq, with a view to facilitating the implementation of this analysis method in the diagnostic setting.
Objectives:
Determine the prevalence of variants with a deleterious effect at RNA level, identified by transcriptomic analysis (RNAseq) in diagnostically errant patients with neonatal hypotonia and/or intellectual disability. This analysis will be carried out in parallel on blood and fibroblast culture (skin biopsy).
Compare the number of pathogenic variants identified by RNAseq on blood tissue with the number of pathogenic variants identified by RNAseq on fibroblast culture. The result will help to decide whether a single sample is sufficient to obtain a diagnosis in patients in diagnostic limbo.
Study endpoints:
The number of patients initially in diagnostic errancy in whom a deleterious variant at RNA level was identified by transcriptomic analysis (RNAseq).
The number of deleterious RNA variants identified in patients in diagnostic errancy using ARNseq on fibroblasts and the deleterious RNA variants identified using ARNseq on blood samples.
Study design:
Multicentric descriptive prevalence study
Study Procedures:
Patients (or their parents in the case of minors) will be informed of the possibility of participating in the study during a follow-up consultation as part of their usual care. Patients will also be given a leaflet explaining the study. After a period of reflection, patients will be seen at one of three centers (Marseille, Toulon, Nice) to sign a consent form and take samples.
Only one visit is planned as part of the study. This is the inclusion visit, during which skin and blood samples are taken.
If a pathogenic variant explaining the phenotype is identified in a patient, the patient's physician will request confirmation of the variant by targeted analysis (Sanger sequencing) by the laboratory (Laboratoire de Génétique Moléculaire, APHM) as part of the diagnosis. This result will be provided by the patient's doctor as part of the patient's usual care.
Subjects number: 62
Study Timelines:
Inclusion period: 36 months Duration of follow-up: There is no follow-up for the patient in this study - a single inclusion visit is planned. Results will be reported as part of the patient's usual care.
Duration of analyses: 6 months Total duration (duration of inclusion and duration of analysis): 42 months
592 studies on the registry are indexed under Rare Diseases; 125 are open to participants now.
This study's planned enrollment of 62 is above the median of 45 across 339 interventional studies indexed under Rare Diseases.
Browse Rare Diseases studies →Assistance Publique Hopitaux De Marseille is the lead sponsor of 702 studies on the registry; 139 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients enrolled in the experimental arm will be seen in consultation to sign the consent form and take samples at one of the participating investigational sites. Only one visit is planned as part of the study. This is the inclusion visit, during which skin and blood samples are taken. If a pathogenic variant explaining the phenotype is identified in a patient, the clinician following the patient will request confirmation of the variant by targeted analysis (Sanger sequencing) as part of the diagnosis. This result will be returned by the clinician who follows the patient as part of his or her usual care.
Procedure: Blood collection · Procedure: skin biopsy
Blood is collected in order to perform transcriptomic sequencing from blood
A biopsy of skin is performed in order to perform transcriptomic sequencing on fibroblasts obtained from the biopsy
Patients with identified deleterious variant at RNA level
The number of patients initially in diagnostic errancy in whom a deleterious variant at RNA level was identified by transcriptomic analysis (RNAseq).
Time frame: Through study completion, an average of 42 month.
Comparison of the number of variants obtained from blood and from fibroblasts
Number of deleterious RNA variants identified in patients with diagnostic errancy using ARNseq on fibroblasts and deleterious RNA variants identified using ARNseq on blood samples
Time frame: Through study completion, an average of 42 month.
Plan to share: No
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