LINKAGE ANALYSIS OF IDIOPATHIC GENERALIZED EPILEPSY (IGE) AND MARKER LOCI ON CHROMOSOME-6P IN FAMILIES OF PATIENTS WITH JUVENILE MYOCLONIC EPILEPSY - NO EVIDENCE FOR AN EPILEPSY LOCUS IN THE HLA REGION

Evidence for a locus (EJM1) in the HLA region of chromosome 6p predisp osing to idiopathic generalized epilepsy (IGE) in the families of pati ents with juvenile myoclonic epilepsy (JME) has been obtained in two p revious studies of separately ascertained groups of kindreds. Linkage analysis has been undertaken in a third set of 25 families including a patient with JME and at least one first-degree relative with IGE. Fam ily members were typed for eight polymorphic loci on chromosome 6p: F1 3A, D6S89, D6S109, D6S105, D6S10, C4B, DQA1/A2, and TCTE1. Pairwise an d multipoint linkage analysis was carried out assuming autosomal domin ant and autosomal recessive inheritance and age-dependent high or low penetrance. No significant evidence in favor of linkage was obtained a t any locus. Multipoint linkage analysis generated significant exclusi on data (lod score < -2.0) at HLA and for a region 10-30 cM telomeric to HLA, the extent of which varied with the level of penetrance assume d. These observations indicate that genetic heterogeneity exists withi n this epilepsy phenotype.