Maria Puiu, Dan Dorica, Raluca Dumache, Gabriela Anton, Natalia Cucu


The aim of our study 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. Materials and Methods. The study 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 study 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. Results. Due to high mortality and morbidity associated with PSW/AS, this study 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. The Romanian PWS association is involved in PC 6 (The European Prader-Willi Syndrome Clinical and Basic Science Research), project that identifies and pulls together different national teams involved in these topics. The medical research in rare genetic disease supposes to be multicentric and even international due to the limitted number of cases. To avoid bias we need large series of patients, to assure statistically correct answers necessary for developing international good practice standards. Conclusion. The research from Romania should be more active in the rare disease area, that's why we propose an epigenetic new European approach realized by prestigious teams. Through this new type of partnership between universities, research institutes, hospitals, nongovernmental associations of affected patients we try to redefine connections between fundamental research and the medical practice, developing a multidisciplinary investigation model for rare disease in Romania. Our study benefits of the applicative research experience of some research teams from the Faculty of Biology in Bucharest and The National Institute of Virology. Research on animals brings many benefits to human medicine and has a decisive role in understanding the etiological mechanisms of some diseases.


Prader- Willi /Angelman syndromes; uniparental disomy; imprinting; epigenetic processes

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