LINKAGE ANALYSIS OF IDIOPATHIC GENERALIZED EPILEPSY IN FAMILIES OF PROBANDS WITH JUVENILE MYOCLONIC EPILEPSY AND MARKER LOCI THE REGION OF EPM-1 ON CHROMOSOME 21Q - UNVERRICHT-LUNDBORG DISEASE AND JME ARE NOT ALLELIC VARIANTS

The locus for Unverricht-Lundborg disease, EPM 1, has recently been ma pped to chromosome 21q22.3. A locus, EJM 1, predisposing to idiopathic generalised epilepsy in families of probands with juvenile myoclonic epilepsy has been localised to chromosome 6p by evidence of linkage to the HLA region. However, segregation analysis suggests a two-locus mo del for JME and evidence has been obtained for genetic heterogeneity w ithin the JME/IGE phenotype. EPM 1 was therefore investigated as a can didate locus in the set of families segregating for IGE and JME which do not show linkage to markers on chromosome 6p. Linkage analysis was carried out in 25 families using three microsatellite DNA markers arou nd the EPM 1 gene region using different models of inheritance. Multip oint linkage analysis provided definite exclusion for 20cM around PFKL , the closest linked marker to EPM 1, under three out of four models t ested. These results strongly suggest that the EPM 1 gene is not Linke d to the phenotype expressed in these families, and therefore that Unv erricht-Lundborg disease and juvenile myoclonic epilepsy are not allel ic variants.