Multi-omics in MECP2 duplication syndrome patients and carriers.
MECP2
MECP2 duplication
RNAseq
Rett syndrome
TMT‐mass spectrometry
Journal
The European journal of neuroscience
ISSN: 1460-9568
Titre abrégé: Eur J Neurosci
Pays: France
ID NLM: 8918110
Informations de publication
Date de publication:
15 May 2024
15 May 2024
Historique:
revised:
16
04
2024
received:
16
01
2024
accepted:
24
04
2024
medline:
15
5
2024
pubmed:
15
5
2024
entrez:
15
5
2024
Statut:
aheadofprint
Résumé
MECP2 duplication syndrome (MDS) is an X-linked neurodevelopmental disorder caused by the gain of dose of at least the genes MECP2 and IRAK1 and is characterised by intellectual disability (ID), developmental delay, hypotonia, epilepsy and recurrent infections. It mainly affects males, and females can be affected or asymptomatic carriers. Rett syndrome (RTT) is mainly triggered by loss of function mutations in MECP2 and is a well described syndrome that presents ID, epilepsy, lack of purposeful hand use and impaired speech, among others. As a result of implementing omics technology, altered biological pathways in human RTT samples have been reported, but such molecular characterisation has not been performed in patients with MDS. We gathered human skin fibroblasts from 17 patients with MDS, 10 MECP2 duplication carrier mothers and 21 patients with RTT, and performed multi-omics (RNAseq and proteomics) analysis. Here, we provide a thorough description and compare the shared and specific dysregulated biological processes between the cohorts. We also highlight the genes TMOD2, SRGAP1, COPS2, CNPY2, IGF2BP1, MOB2, VASP, FZD7, ECSIT and KIF3B as biomarker and therapeutic target candidates due to their implication in neuronal functions. Defining the RNA and protein profiles has shown that our four cohorts are less alike than expected by their shared phenotypes.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Instituto de Salud Carlos III
Organisme : European Social Fund and the Government of Catalonia
ID : 2020 FI-B 00888
Organisme : Spanish Ministry of Health
ID : PI20/00389
Organisme : Síndrome duplicación MECP2: Miradas que hablan
ID : PFNR0085
Organisme : Spanish Ministry of Science, Innovation and Universities
ID : FPU18/02152
Informations de copyright
© 2024 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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