THE GENE FOR A RECESSIVELY INHERITED HUMAN CHILDHOOD PROGRESSIVE EPILEPSY WITH MENTAL-RETARDATION MAPS TO THE DISTAL SHORT ARM OF CHROMOSOME-8

A recently delineated childhood epilepsy has hitherto been observed on ly in a small geographic region in northern Finland, where, with the e xception of one, both parents of all of the 11 sibships with affected individuals descend from one or two founding couples. The disease is c haracterized by generalized tonic-clonic seizures with onset at 5-10 y ears and progressive, severe mental retardation with onset 2-5 years a fter the first seizures. In this study the gene locus is assigned to t he telomeric region of chromosome 8p by linkage. Analyses of recombina tions place the locus in the 7-centimorgan interval between AFM185xb2 and D8S262 in which three markers, D8S504, D8S264, and AFM077yg5, show no recombinations with the phenotype. Haplotypes comprising alleles a t the above five loci support the hypothesis of a single founding muta tion for all affected chromosomes except the one belonging to the unre lated parent, who has a very different haplotype, suggesting another m utation or a very old ancestry of a single mutation. This study raises to three the number of heritable epilepsies whose gene loci have been mapped and provides a starting point for the cloning of the gene. It also suggests the possibility that the disease might not be limited to the northern Finnish population.