The chromosome 6p epilepsy locus: exploring mode of inheritance and heterogeneity through linkage analysis

Juvenile myoclonic epilepsy (JME) is a common form of adolescent-onset, generalized epilepsy. JME is genetically linked to the HLA locus on chromosome 6. Families of JME patients also have a significant recurrence of other forms of generalized epilepsy. We used the linkage data to investigate the mode of inheritance of JME and the associated electroencephalographic (EEG) traits at the HLA-linked locus. We investigated how robust the linkage results were when we changed the assumptions of mode of inheritance and penetrance and whether absence and clonic-tonic-clonic in JME families are influenced by the same gene locus as JME. Our results show that the finding of linkage is stable within a wide range of assumptions of penetrance and mode of inheritance, and that the EEG traits seen in unaffected family members reflect the actions of the same gene that is involved in the expression of JME. Our data also suggest that the same locus is responsible for non-JME forms of epilepsy seen in JME families, and that either different doses of the disease allele at the JME locus may lead to different epilepsy phenotypes or that another locus influences the final disease phenotype.