Northern epilepsy, a new member of the NCL family

Northern epilepsy, or progressive epilepsy with mental retardation (EPMR), is an autosomal recessive disorder characterized by normal early developmen t, onset of generalized tonic-clonic seizures between the ages of 5 and 10 years, and subsequent progressive mental retardation. The seizures increase in frequency until puberty after which the epileptic activity starts to de cline. Mental retardation begins 2-5 years after the onset of seizures and continues through adulthood. Neuropathological findings have shown that EPM R is a new member (CLN8) of the neuronal ceroid lipofuscinosis (NCL) group of neurodegenerative disorders. The CLN8 gene was identified recently. It e ncodes a 286 amino acid putative transmembrane protein with no homology to previously known proteins. Subsequently, the homologous mouse gene (Cln8) w as sequenced and localized to the region of the mouse genome linked to moto r neuron degeneration, mouse mnd. Mnd is a naturally occurring mouse mutant with intracellular autofluorescent inclusions similar to those seen in hum an CLN8. A mutation in mnd mouse DNA was identified, indicating that mnd is a murine model for CLN8.