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Diagnosis of RSTS: Identification of the Acetylation Profiles as Epigenetic Markers for Assessing Causality of CREBBP and EP300 Variants.

NCT04122742 · Status: RECRUITING · Type: OBSERVATIONAL · Enrollment: 154

Last updated 2024-01-17

No results posted yet for this study

Summary

Rubinstein-Taybi syndrome (RSTS) is a rare and severe congenital developmental disorder characterized by congenital anomalies and intellectual disability with a long term memory deficit. The main challenge is to improve the intellectual and memory efficiency of these patients. CREBBP and EP300 are the two genes known to cause RSTS. Both paralogs play a major role in chromatin remodeling and encode for transcriptional co-activators interacting with many proteins.

The aim of this pilot study is to characterize the histone acetylation profiles in order to identify specific acetylation markers during normal and pathological neuronal differentiation of cortical and pyramidal neurons in RSTS.

Conditions

  • Rubinstein-Taybi Syndrome

Interventions

PROCEDURE

skin biopsy for the primary fibroblast culture and a 15 ml blood sample (3 unnamed samples of 5ml) in each of the 4 SRT patients included.

Performed with a 3 mm diameter punch under local anesthesia. The procedure can be done in a consultation office respecting a strict asepsis.

OTHER

Generation of Induced Pluripotent Stem Cells (iPSC) from fibroblasts obtained by skin biopsy

induced Pluripotent Stem Cells (iPSC) production of patients with CREBBP mutation and differentiation into cortical neurons and pyramidal neurons

OTHER

Histone acetylation profiles of cells of SRT patients with CREBBP mutations

Study of acetylome by liquid chromatography coupled with tandem mass spectrometry (LC-MS / MS) Validation of specific acetylation targets by ChIP-Sequencing

OTHER

Functional involvement of identified epigenetic alterations

Transcriptome analysis with RNA-Seq Generation of isogenic iPSC clones by correction of CREBBP mutations in SRT patients by CrispR-Cas9.

BIOLOGICAL

Culture of lymphoblastoid line from blood sample

Achievement of a ficoll Culture of lymphoblasts and conservation Establishment of lymphoblastoid line and conservation

Sponsors & Collaborators

  • University Hospital, Bordeaux

    lead OTHER

Eligibility

Min Age
2 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2019-10-08
Primary Completion
2025-10-31
Completion
2025-10-31

Countries

  • France

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04122742 on ClinicalTrials.gov