Corelation of clinic, genetic and epigenetic aspects implicated in the etiology of Prader Willi/Angelman syndroms: model of multidisciplinary abordation for rare diseases in Romania

Submitted by alexandra persa on Thu, 03/29/2012 - 21:12
Romanian Prader Willi Association is a partner in this project coordinated by Medical university Timisoara.
The aim of the project is the integration of a multidisciplinary approach for Prader Willi and Angelman syndromes, distinct genomic diseases, with a neurodegenerative component. The main lesion is localized on the 15q11.2-13 chromosome caused during genitors´ gametogenesis and reproduction process. This deficiency may be represented by deletion, uniparental disomy and altered epigenetic marking through DNA methylation or chromatin modification. Both diseases are caused by changes in parent contributions on the aforementioned region. The modifications in imprinting diseases like Prader Willi and Angelman, require: the study of regional regulation for genetic/epigenetic processes in clusters; the contribution of specific genes regulating the imprinting of cluster formation; enhancer activity, the DNA and chromatin replication timing, as well as correspondence between histones, protein complexes, iRNA and epigenetic processes from DNA. The project envisages the cytogenetic and molecular genetics approaches in the syndromes diagnosis, establishing a European research network partnership.
The research will enable: 1. establishment of a strategy in definition for genotypes PWS/AS, 2. correct identification of the genetic defect, 3. desciphering the variation in gene expression/ gene subsequention and their regulation pathway mechanism, 4. the involvement of epigenetic factors that modulate (enhancing/decreasing) the severity of phenotypic aspects into the diagnosis protocols. The project envisages the understanding of early development processes and hopefully will contribute to elucidate the basic mechanisms determining the clinical classical modifications. Creation of a database will permit the collection of clinical, genetic and epigenetic data from Romania and further the integration into the European data base. Due to high mortality and morbidity associated with PSW/AS, this project will be the ground for new clinical studies to establish guidelines for diagnosis and treatment in order to improve the quality of medical practice and an improvement of medical and social standard for affected patients with PWS/AS.