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Multi-omics in MECP2 duplication syndrome patients and carriers.
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  • Ainhoa Pascual-Alonso,
  • Clara Xiol,
  • Dmitrii Smirnov,
  • Robert Kopajtich,
  • Holger Prokisch,
  • Judith Armstrong
Ainhoa Pascual-Alonso
Fundació per la Recerca Sant Joan de Déu
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Clara Xiol
Fundació per la Recerca Sant Joan de Déu
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Dmitrii Smirnov
Technical University of Munich
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Robert Kopajtich
Technical University of Munich
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Holger Prokisch
Technical University of Munich
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Judith Armstrong
Institut de Recerca Sant Joan de Deu

Corresponding Author:[email protected]

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Abstract

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 MDS patients. We gathered human skin fibroblasts from 17 patients with MDS, 10 MECP2 duplication carrier mothers and 21 RTT patients, 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.