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Diagnosis of RSTS: Identification of the Acetylation Profiles as Epigenetic Markers for Assessing Causality of CREBBP and EP300 Variants. (GENEPI)
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.
Details
| Lead sponsor | University Hospital, Bordeaux |
|---|---|
| Status | UNKNOWN |
| Enrolment | 154 |
| Start date | 2019-10-08 |
| Completion | 2025-10 |
Conditions
- Rubinstein-Taybi Syndrome
Interventions
- 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.
- Generation of Induced Pluripotent Stem Cells (iPSC) from fibroblasts obtained by skin biopsy
- Histone acetylation profiles of cells of SRT patients with CREBBP mutations
- Functional involvement of identified epigenetic alterations
- Culture of lymphoblastoid line from blood sample
Primary outcomes
- Identification of a specific acetylation profile of RSTS — Inclusion visit
From skin biopsy sample collected at inclusion visit : * No assumptions about the number of histone marks needed to define the profile * Will be retained as the specific mark of the disease if it is 100% present in the cases and 100% absent in the controls * The specific profile can be defined in one or more stages of cell differentiation: iPSC - neuronal progenitor - cortical and pyramidal neurons
Countries
France