LINKAGE ANALYSIS OF JUVENILE MYOCLONIC EPILEPSY AND MICROSATELLITE LOCI SPANNING 61 CM OF HUMAN-CHROMOSOME 6P IN 19 NUCLEAR PEDIGREES PROVIDES NO EVIDENCE FOR A SUSCEPTIBILITY LOCUS IN THIS REGION

Linkage analysis in separately ascertained families of probands with j uvenile myoclonic epilepsy (JME) has previously provided evidence both for and against the existence of a locus (designated ''EJM1''), on ch romosome 6p, predisposing to a trait defined as either clinical JME, i ts associated electroencephalographic abnormality, or idiopathic gener alized epilepsy. Linkage analysis was performed in 19 families in whic h a proband and at least one first- or two second-degree relatives hav e clinical JME. Family members were typed for seven highly polymorphic microsatellite markers on chromosome 6p: D6S260, D6S276, D6S291, D6S2 71, D6S465, D6S257, and D6S254. Pairwise and multipoint linkage analys is was carried out under the assumptions of autosomal dominant inherit ance at 70% and 50% penetrance and autosomal recessive inheritance at 70% and 50% penetrance. No significant evidence in favor of linkage to the clinical trait of JME was obtained for any locus. The region form ally excluded (LOD score <-2) by using multipoint analysis varies depe nding on the assumptions made concerning inheritance parameters and th e proportion of linked families, alpha - that is, the degree of locus heterogeneity. Further analysis either classifying all unaffected indi viduals as unknown or excluding a subset of four families in which pyk noleptic absence seizures were present in one or more individuals did not alter these conclusions.