CLONING OF THE GENE RESPONSIBLE FOR AND AUTOSOMAL RECESSIVE EPILEPSY OF INFANCY

The study is aimed to identify the gene responsible for a familial form of idiopathic myoclonic epilepsy of infancy (FIME). The disease is transmitted by healthy parents (carrier) to 25% of sibs as autosomal recessive trait. Distinctive clinical features of FIME are febrile seizures in infancy and early childhhod, long-lasting myoclonic seizures that may to persist in adulthood and rare generalized seizures. Previous studies led us to localize the mutated gene to chromosome 16. The present proposal is aimed to clone the disease gene by: - refining the critical regions harbouring the mutated genes by the analysis of recombinations and ancestral haploypes. - analyzing the sequences available from the Human Genome Project and developing transcriptional maps of the regions. - selecting genes that are potentially involved in epileptogenesis. - sequencing the coding region of candidate genes in affected individuals. The project has a great significance as far as no genes have been associated to any idiopathic recessive epilepsy. The identification of the mutated genes could disclose new insight into pathogenesis of epilepsy. To date the only genes that have been found mutated in epilepsy encode for proteins constituting neuronal ion channels and are specifically associated to dominant idiopathic or sporadic epilepsies. The cloning of the FIME gene could also led to the development of genetic tests with great benefits for differential diagnosis of myoclonic epilepsies of infancy and genetic counselling.