Reference:
5
Abstract:
The acute phase of regression (6-12 months) of Rett syndrome coincides with the period of childhood vaccinations. Data that come both from our own experience and from the literature indicate that different RTT girls were initially classified as suffering from encephalopathy for damage caused by the vaccine (Moeschler JB, et al, 1988) (A. Fiumara et al 2002) (A. Renieri, data not unpublished). These data seem to suggest that Rett syndrome is caused only by the mutation in the MECP2, by other factors. That lead to the hypothesis that mutations in MECP2 is necessary but not sufficient for the development of the disease. In agreement with this hypothesis, it was recently shown that pathogenic mutations in the MECP2 have been identified in a proportion of infants (about 3.5%), much higher than the prevalence of the disease (less than 1:10,000) (J. Yu, ASHG 2010 meeting). We therefore hypothesized that Rett syndrome can develop only in people with mutations in MECP2, combined with the presence of particular alleles of the HLA system. This structure may induce a dysfunction of the immune system that could lead to an abnormal response in the case of vaccination. In fact, several studies in the literature have led to attribute to the MECP2 important functions in the development and regulation of the immune system (D Balmer et al. 2002) (Y Tong et al. 2005) (Lal G et al. 2009) (R Webb et al. 2009) (Plioplys AV et al. 1994) (Fiumara A et al. 1999) (Szabo SJ et al. 2000) (T Tanioka et al. 2005) (Delgado IJ et al. 2006) (Lintas C et al . 2011). Taken together, these results led to the hypothesis for the origin immune Rett and to indicate the immune system as a potential therapeutic target (Derecki NC et al 2010). We propose to perform the typing of HLA genes in a large series of Rett patients (233 patients with a mutation in the MECP2) and see if the gene frequency may deviate significantly from the frequency in the Italian population characterized in order to determine whether some of the genes HLA system can determine or influence the severity of the RTT phenotype. PURPOSE ‘OF THE PROJECT: In this project, we propose the characterization of HLA in patients with mutated MECP2 in order to: investigate whether there is a correlation with the onset of Rett syndrome; check whether there is a correlation with the severity of the disease.
PROJECT DETAILS
beginning: 2010.
end: 2011.
Country of research: Italy
Counry of funding source: Italy
Funding organization: AIRETT
Financing: PRIVATE FUNDERS – 75 000 €