EXCLUSION OF LINKAGE OF GENETIC FOCAL SHARP WAVES TO THE HLA REGION ON CHROMOSOME-6P IN FAMILIES WITH BENIGN PARTIAL EPILEPSY WITH CENTROTEMPORAL SHARP WAVES

Benign partial epilepsy with centrotemporal sharp waves (benign roland ic epilepsy, BRE) is a common form of idiopathic, localisation-related epilepsy of childhood. The characteristic age-dependent focal sharp w ave (fsw) found on the EEG in this disorder segregates as an autosomal dominant trait in families with probands with BRE and acts as a neuro biological marker for the increased risk of developing BRE, other beni gn partial epilepsies of childhood, and other developmental disorders in these families. One of the genes for idiopathic generalised epileps y (IGE), designated EJM1, has been mapped in families with probands wi th juvenile myoclonic epilepsy, by linkage to the HLA region on chromo some 6. As BRE and IGE are benign, idiopathic, age-dependent epilepsie s, EJM1 is a candidate locus for the fsw underlying BRE and related di sorders. Genetic linkage analysis was undertaken in 11 families with p robands with BRE and one or more first degree relatives with fsw, with or without BRE, using a polymorphic DNA marker within the HLA region. Apparently unaffected individuals were classed as affection status un known. Assuming autosomal dominant inheritance with a penetrance of 0. 9 gave a lod score of -2.3 at zero recombination, excluding the candid ate gene region around HLA. These observations exclude an important ca ndidate gene for this common disorder, and suggest a fundamental molec ular and genetic distinction between the benign partial epilepsies of childhood and the idiopathic generalised epilepsies.