Rare Genetic DiseaseARNseqFibroSanNCT07075107
Transcriptomic Analysis of Fibroblasts and Blood in Patients With Rare Diseases
A study testing Blood collection and skin biopsy in people with Rare Genetic Disease, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 0 to 99 years
- Conditions the study is for
- Rare Genetic Disease
- What is being tested?
- Blood collection and skin biopsy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteFrance
- Study dates
- 9 Mar 2026to 30 Apr 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 99 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Male or female, aged 0-99 years
- Patient with neonatal intellectual disability and/or hypotonia followed at one of three inclusion centers
- Patient or parent has been informed about the study and has signed an informed consent form
- Genetic analysis by high-throughput DNA sequencing (gene panel, exome, genome) did not identify any abnormality explaining the patient's phenotype.
- If the patient's phenotype is suggestive of Prader-Willi syndrome or Angelman syndrome: a methylation anomaly test on chromosome 15 was negative.
- If the patient's phenotype is suggestive of fragile X syndrome: a repeat expansion analysis of the FMR1 gene was negative.
- If the patient's phenotype is suggestive of myotonic dystrophy type I, DM1: a repeat expansion analysis of the DMPK gene was negative.
- Patient entitled to or beneficiary of a social security scheme
Who cannot join
- Patient deprived of liberty
- Pregnant or breast-feeding woman,
- The person required to sign the consent form does not understand French
- Person under guardianship and/or curatorship
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Assistance publique - hôpitaux de Marseille
Marseille, Provence-Alpes-Côt-d'Azue, 13354
Svetlana GOROKHOVA, MD, 33491388499, svetlana.gorokhova@ap-hm.fr
Svetlana GOROKHOVA, MD
About this study
Official title: Transcriptomic Analysis (RNAseq) of Blood and Fibroblasts to Establish a Diagnosis in Patients With Rare Diseases
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.
Read the detailed description
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
- Conditions
- Rare Genetic Disease
- Being tested
- Blood collection, skin biopsy
- Keywords
- genetic analysis by high-throughput DNA sequencing, ARNseq, transcriptomic data, interpretation of sequence variants, Genomic Testing, RNA sequencing data, transcriptome analysis in rare disease, Rare diseases, Intellectual disability
- Medical subject headings
- Rare Diseases, Intellectual Disability
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood collectionProcedure or surgery
Blood is collected in order to perform transcriptomic sequencing from blood
skin biopsyProcedure or surgery
A biopsy of skin is performed in order to perform transcriptomic sequencing on fibroblasts obtained from the biopsy
| Study group | Role | What they receive |
|---|---|---|
| ARNseq | Experimental | 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. Receives: Procedure: Blood collection; Procedure: skin biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Through study completion, an average of 42 month.
Secondary outcomes (1)
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
Measured: Through study completion, an average of 42 month.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2025
- Study start9 Mar 2026
- Primary completion30 Apr 2029 (estimated)
- Study completion30 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rare Genetic DiseaseStudies of the same condition, open and under way.
- More trials run by Assistance Publique Hopitaux De MarseilleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique Hopitaux De Marseille
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07075107
- Sponsor's protocol ID
- RCAPHM23_0469
- Other IDs
- ID-RCB
- Acronym
- ARNseqFibroSan
- Status last verified
- May 2026
- First submitted
- 22 May 2025
- Last updated
- 8 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Transcriptomic Analysis (RNAseq) of Blood and Fibroblasts to Establish a Diagnosis in Patients With Rare Diseases
- ClinicalTrials.gov ID
- NCT07075107
- Acronym / sponsor ID
- ARNseqFibroSan / RCAPHM23_0469
- Conditions
- Rare Genetic Disease
- Keywords
- genetic analysis by high-throughput DNA sequencing, ARNseq, transcriptomic data, interpretation of sequence variants, Genomic Testing, RNA sequencing data, transcriptome analysis in rare disease, Rare diseases
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- Assistance Publique Hopitaux De MarseilleUniversity, hospital or other
- Study start
- 9 Mar 2026 (actual)
- Primary completion
- 30 Apr 2029 (estimated)
- Study completion
- 30 Apr 2029 (estimated)
- First posted
- 20 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ARNseq | Experimental | Procedure: Blood collection, Procedure: skin biopsyPatients 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. |
Who may qualify
- Ages
- 0 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female, aged 0-99 years
- Patient with neonatal intellectual disability and/or hypotonia followed at one of three inclusion centers
- Patient or parent has been informed about the study and has signed an informed consent form
- Genetic analysis by high-throughput DNA sequencing (gene panel, exome, genome) did not identify any abnormality explaining the patient's phenotype.
- If the patient's phenotype is suggestive of Prader-Willi syndrome or Angelman syndrome: a methylation anomaly test on chromosome 15 was negative.
Key exclusion criteria (4 listed)
- Patient deprived of liberty
- Pregnant or breast-feeding woman,
- The person required to sign the consent form does not understand French
- Person under guardianship and/or curatorship
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood collectionBlood is collected in order to perform transcriptomic sequencing from blood | Procedure or surgery | ARNseq |
| skin biopsyA biopsy of skin is performed in order to perform transcriptomic sequencing on fibroblasts obtained from the biopsy | Procedure or surgery | ARNseq |
Primary outcome
Patients with identified deleterious variant at RNA level
Time frame: Through study completion, an average of 42 month.
The number of patients initially in diagnostic errancy in whom a deleterious variant at RNA level was identified by transcriptomic analysis (RNAseq).
1 secondary outcome
Comparison of the number of variants obtained from blood and from fibroblasts
Time frame: Through study completion, an average of 42 month.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood collection and skin biopsy in people with Rare Genetic Disease, run by Assistance Publique Hopitaux De Marseille at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Svetlana GOROKHOVA, MD (33491388499, svetlana.gorokhova@ap-hm.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Patients with identified deleterious variant at RNA level (time frame: Through study completion, an average of 42 month.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2026.