Clinical study of heterogeneity in a large cohort of patients with Rett syndrome using a molecular-biochemical approach.

Reference:
3

Abstract:
Rett syndrome (RTT, MIM 312750) is a progressive neurodevelopmental disorder that has an incidence of 1:10,000 people are female. Despite the identification of three genes involved (MECP2, CDKL5 and FOXG1), the pathogenesis of the syndrome is not known to date. The study presented here aims to: deepen the existing knowledge base of the pathogenetic mechanisms responsible for Rett syndrome; identify neurological and biochemical pathways altered in Rett syndrome; identify factors modifiers of the clinical picture in all its aspects in order to be able to point to a possible therapeutic treatment of the syndrome; identify new causative genetic defects of the syndrome. Such objectives will be achieved through the evaluation: of genes differentially expressed significantly in a large cohort of patients Rett Representative for mutation type and phenotype; of differentially methylated regions significantly in the same cohort; the correlation: phenotype in its entirety (global severity scale) and significant differences in the expression of genes related to specific pathways regulated by MeCP2, epileptic phenotype and no significant differences in the expression of genes related to specific pathways regulated by Mecp2, phenotype in its entirety and no significant differences in methylation of regions of the genome (epigenetic changes), the epileptic phenotype and significant differences in the methylation of regions of the genome (epigenetic changes); checking the status of oxidative stress and defects in the expression levels of metallothionein (MT) in the blood; extensive sequencing of patients without the genetic defect (negative screening of MECP2, CDKL5 and FOXG1).

PROJECT DETAILS 

beginning: 2010.

end: 2011.

Country of research: Italy

Counry of funding source: Italy

Funding organization: AIRETT

Financing: PRIVATE FUNDERS – 60 000 €

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