Juvenile myoclonic epilepsy (JME) is among the commonest of the childhood epilepsies. Despite the recognition of strong genetic factors, molecular characterization of JME has thus far been unsuccessful. This may be due, in part, to genetic and clinical heterogeneity that is present in this disorder. Familial adult myoclonic epilepsy (FAME) is a rare idiopathic generalized epilepsy characterized by autosomal dominant inheritance, adult onset, varying degrees of myoclonus in the limbs, rare tonic-clonic seizures and a benign course. We have recently localized a gene for this disorder to chromosome 8q24.1. The objective of this research is to identify the gene responsible for FAME and to characterize the protein's role in this disorder specifically and in neuroexcitability more generally. This objective will be attained using several concurrent methods. First, the region corresponding to the FAME locus is being positionally cloned using bacterial artificial chromosomes and cosmids. Secondly, new polymorphic markers will be examined across the region to identify a shared haplotype between our FAME families. Finally, putative cDNAs identified through the EST database or through screening cDNA libraries, will be examined for mutations. Upon the identification of the FAME gene, appropriate cellular, biochemical, and physiological investigations will be performed to characterize the function of the FAME protein. Mouse models of FAME can then be created and will allow investigations of pathogenesis in vivo. These experiments will take place in a molecular genetics laboratory geared specifically towards experiments of this nature.
|Russell, Jonathan F; Fu, Ying-Hui; Ptá?ek, Louis J (2013) Episodic neurologic disorders: syndromes, genes, and mechanisms. Annu Rev Neurosci 36:25-50|
|Russell, Jonathan F; Steckley, Jamie L; Coppola, Giovanni et al. (2012) Familial cortical myoclonus with a mutation in NOL3. Ann Neurol 72:175-83|
|Zhang, Luoying; Jones, Chris R; Ptacek, Louis J et al. (2011) The genetics of the human circadian clock. Adv Genet 74:231-47|