Objective Progressive Myoclonus Epilepsy (PME) of the Lafora type is an autosomal recessive disease, which presents in teenage years with myoclonia and generalized seizures leading to death within a decade of onset. Using a genetic and functional genomic approach we are studying the biology of LD (Lafora Disease) with the goal of being able to offer better treatment and possible a cure for this fatal disease.Using a positional cloning approach, two genes causing LD, EPM2A on chromosome 6q24 and recently EPM2B on chromosome 6p22.3 (the applicant is one of the authors), were identified. EPM2A encodes a novel protein, laforin, with the only clue to its function being that it contains a carbohydrate-binding domain (CBD) in the N-terminus and a protein tyrosine phosphatase (PTP) domain in the C-terminus.EPM2B encodes a novel protein, malin, containing a zinc finger of the RING type in the N-terminal half and 6 NHL-repeat domains in the C-terminal direction. Three laforin interacting proteins were recently isolated, EPM2AIP 1 of unknown function, HIRIP5 that may be involved in iron homeostasis, and R5, a glycogen targeting regulatory subunit of Phosphoprotein Phosphatase-1, but their roles in the disease still need to be clarified.To gain insight into the possible role of these proteins in the pathology of the disease we are working to verify whether they are part of the same pathway and to identify other interacting proteins using yeast two-hybrid screens, immunoprecipitation and GST pull-down experiments.During the course of the study we have identified that further genetic heterogeneity exists for LD (some families do not harbour mutations in EPM2A and EPM2B) and we are currently working to identify the third disease-causing gene (EPM2C). Fields of science medical and health sciencesbasic medicineneurologyepilepsynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepathologynatural sciencesbiological sciencesgeneticschromosomesmedical and health sciencesbasic medicinephysiologyhomeostasis Programme(s) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Topic(s) MOBILITY-4.2 - Marie Curie International Reintegration Grants (IRG) Call for proposal FP6-2002-MOBILITY-12 See other projects for this call Funding Scheme IRG - Marie Curie actions-International re-integration grants Coordinator FONDAZIONE MALATTIE RARE "MAURO BASCHIROTTO" Address Via b.bizio, 1 Costozza di longare (vicenza) Italy See on map Links Website Opens in new window EU contribution € 0,00
