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dc.contributor.authorShovlin, Stephen
dc.contributor.authorTropea, Daniela
dc.date.accessioned2019-04-25T10:09:15Z
dc.date.available2019-04-25T10:09:15Z
dc.date.issued2018-07-11
dc.identifier.issn1750-1172
dc.identifier.pmid29996871
dc.identifier.doi10.1186/s13023-018-0857-8
dc.identifier.urihttp://hdl.handle.net/10147/624168
dc.description.abstractThe mechanisms of neuro-genetic disorders have been mostly investigated in the brain, however, for some pathologies, transcriptomic analysis in multiple tissues represent an opportunity and a challenge to understand the consequences of the genetic mutation. This is the case for Rett Syndrome (RTT): a neurodevelopmental disorder predominantly affecting females that is characterised by a loss of purposeful movements and language accompanied by gait abnormalities and hand stereotypies. Although the genetic aetiology is largely associated to Methyl CpG binding protein 2 (MECP2) mutations, linking the pathophysiology of RTT and its clinical symptoms to direct molecular mechanisms has been difficult. One approach used to study the consequences of MECP2 dysfunction in patients, is to perform transcriptomic analysis in tissues derived from RTT patients or Induced Pluripotent Stem cells. The growing affordability and efficiency of this approach has led to a far greater understanding of the complexities of RTT syndrome but is also raised questions about previously held convictions such as the regulatory role of MECP2, the effects of different molecular mechanisms in different tissues and role of X Chromosome Inactivation in RTT. In this review we consider the results of a number of different transcriptomic analyses in different patients-derived preparations to unveil specific trends in differential gene expression across the studies. Although the analyses present limitations- such as the limited sample size- overlaps exist across these studies, and they report dysregulations in three main categories: dendritic connectivity and synapse maturation, mitochondrial dysfunction, and glial cell activity. These observations have a direct application to the disorder and give insights on the altered mechanisms in RTT, with implications on potential diagnostic criteria and treatments.en_US
dc.description.sponsorshipSS salary was partially supported by Meath Foundation research grant 2015 to L. Gallagher and D. Tropea.en_US
dc.language.isoenen_US
dc.publisherOrphanet Journal of Rare Diseasesen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subjectMethyl-Cpg-binding protein 2en_US
dc.subjectMicroArrayen_US
dc.subjectRNASeqen_US
dc.subjectRett syndromeen_US
dc.subjectTranscriptomicsen_US
dc.subjectGENETIC DISORDERSen_US
dc.subjectRETT SYNDROMEen_US
dc.subjectGENETICSen_US
dc.titleTranscriptome level analysis in Rett syndrome using human samples from different tissues.en_US
dc.typeArticleen_US
dc.identifier.journalOrphanet Journal of Rare Diseasesen_US
dc.description.fundingOtheren_US
dc.description.provinceLeinsteren_US
dc.description.peer-reviewpeer-reviewen_US
dc.source.journaltitleOrphanet journal of rare diseases
refterms.dateFOA2019-04-25T10:09:15Z


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