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Pascual-Alonso, A.* ; Xiol, C.* ; Smirnov, D. ; Kopajtich, R. ; Prokisch, H. ; Armstrong, J.*

Multi-omics in MECP2 duplication syndrome patients and carriers.

Eur. J. Neurosci., DOI: 10.1111/ejn.16389 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Mecp2 ; Mecp2 Duplication ; Rnaseq ; Rett Syndrome ; Tmt‐mass Spectrometry; Rett-syndrome; Mouse Model
ISSN (print) / ISBN 0953-816X
e-ISSN 1460-9568
Journal European Journal of Neuroscience
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Neurogenomics (ING)
Grants Instituto de Salud Carlos III