Study of the Pathophysiology of RNU4ATAC and RTTN Associated Syndromes
NCT ID: NCT06111950
Last Updated: 2024-10-09
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
NA
45 participants
INTERVENTIONAL
2024-08-27
2029-08-27
Brief Summary
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The hypothesis of the study is that U12 genes coding for primary cilia components are particularly sensitive to minor splicing defects caused by RNU4ATAC mutations. Indeed, a child showing signs of TALS but negative for RNU4ATAC was found to carry a homozygous variant in the RTTN gene, coding for the rotatin protein located at the centrosome and the base of the primary cilia and playing a role in maintaining these structures. In addition, bi-allelic RNU4ATAC mutations were identified in five patients presenting with traits suggestive of the Joubert syndrome (JBTS), a well-characterized ciliopathy. These patients also present with traits typical of TALS/RFMN/LWS.
To better understand the causes of these pathologies, a cohort of patients with syndromes associated with bi-allele mutations of the RNU4ATAC or RTTN gene will be gathered, in order to conduct studies on the cells of these patients. Blood samples will be taken, as well as skin biopsies, if possible. These samples will be used to create induced pluripotent stem cell lines. Blood samples will also be collected from the parents of RNU4ATAC patients, to eliminate in transcriptomic analyses expression variations due to differences in genetic background. Biopsies of skin, muscle and brain tissue will be collected on foetuses carrying two-allele RNU4ATAC or RTTN mutations whose parents have had a miscarriage or have chosen to have a medical abortion. The biological samples collected will be used to study the transcription level of U12 genes, the splicing of their pre-messenger RNA, their main cellular functions, and the structural characteristics of tissues and cells.
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SINGLE_GROUP
OTHER
NONE
Study Groups
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RNU4ATAC patient
Patient with bi-allelic mutation of the RNU4ATAC gene
Blood samples
Blood samples of 5 ml to 15 ml depending on their weight
Skin biopsies
Biopsies of fragment of skin 2 to 3 mm long by 1 mm wide and 1 mm deep will preferably be taken on the inside of the arm, in the upper third, between the bend of the elbow and the hollow of the armpit under strict sterility conditions.
RNU4ATAC fetus
Fetus with bi-allelic mutation of the RNU4ATAC gene
Fetal samples
Skin, muscle, brain and bone biopsies will be collected from fetuses in the autopsy room after the medical termination of pregnancy or miscarriage
RNU4ATAC parent
Parent of patient or fetus with bi-allelic mutation of the RNU4ATAC gene and who present themselve mono-allelic mutation of the RNU4ATAC gene
Blood samples
Blood samples of 5 ml to 15 ml depending on their weight
RTTN patient
Patient with bi-allelic mutation of the RTTN gene
Blood samples
Blood samples of 5 ml to 15 ml depending on their weight
Skin biopsies
Biopsies of fragment of skin 2 to 3 mm long by 1 mm wide and 1 mm deep will preferably be taken on the inside of the arm, in the upper third, between the bend of the elbow and the hollow of the armpit under strict sterility conditions.
RTTN fetus
Fetus with bi-allelic mutation of the RTTN gene
Fetal samples
Skin, muscle, brain and bone biopsies will be collected from fetuses in the autopsy room after the medical termination of pregnancy or miscarriage
Interventions
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Blood samples
Blood samples of 5 ml to 15 ml depending on their weight
Skin biopsies
Biopsies of fragment of skin 2 to 3 mm long by 1 mm wide and 1 mm deep will preferably be taken on the inside of the arm, in the upper third, between the bend of the elbow and the hollow of the armpit under strict sterility conditions.
Fetal samples
Skin, muscle, brain and bone biopsies will be collected from fetuses in the autopsy room after the medical termination of pregnancy or miscarriage
Eligibility Criteria
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Inclusion Criteria
* Woman or man
* All ages
* Presence of bi-allelic mutations of RNU4ATAC or RTTN
* Written consent of parents or legal guardian(s)
* Affiliation to a Social Security scheme
Healthy participants (Parent of the patient)
* Woman or man
* Major
* Presence of mono-allelic mutations of RNU4ATAC
* Written consent of the participant
* Affiliation to a Social Security scheme
Parents having recourse to a medical termination of pregnancy or having had a spontaneous miscarriage (for fetus samples)
* Woman or man
* Major
* Presence of bi-allelic mutations of RNU4ATAC or RTTN in the fetus
* Written parental consent
* Affiliation to a Social Security scheme
Exclusion Criteria
ALL
Yes
Sponsors
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Hospices Civils de Lyon
OTHER
Responsible Party
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Locations
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Centre de référence des anomalies du développement et syndromes malformatifs du Sud-Ouest Occitanie Réunion, CHU de Bordeaux-GH Pellegrin
Bordeaux, , France
Centre de référence anomalies du développement de Lyon, Hôpital Femme Mère Enfant
Bron, , France
Centre de référence des anomalies du développement et syndromes malformatifs de l'Est, CHU de DIJON
Dijon, , France
Centre de référence des anomalies du développement et syndromes malformatifs de l'inter région Nord-Ouest, Hôpital J de Flandre
Lille, , France
Unité Fonctionelle d'embryo-fœtopathologie, Hôpital Necker-Enfants Malades
Paris, , France
Centre de référence des anomalies du développement et syndromes malformatifs de l'Ouest, Hôpital Sud
Rennes, , France
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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69HCL20_0599
Identifier Type: -
Identifier Source: org_study_id
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