Genetic and physical mapping of the progressive epilepsy with mental retardation (EPMR) locus on chromosome 8p

Abstract

Progressive epilepsy with mental retardation (EPMR) is an autosomal recessive disorder discovered recently from an isolated region in Finland. The disorder is characterized by normal early development, generalized tonic-clonic seizures with onset at 5-10 years of age, and progressive mental retardation beginning 2-5 years after the onset of seizures. We recently mapped the EPMR locus to a 7-cM region on chromosome 8p between markers AFM185xb2 and D8S262. A recombination detected with a new microsatellite marker AFMa054td9 narrows the region to 4 cM. A yeast artificial chromosome [YAC] contig containing 22 YACs was constructed across the disease gene region. The YAC contig is characterized by a collection of 19 YAC-end sequence-tag sites together with seven microsatellite markers. The entire YAC contig spans a minimum of 3 Mb. Moreover, the distal end of the contig contains a subtelomeric YAC yRM2205 that anchors the contig to the telomere. Construction of a YAC contig across the disease gene region is an essential step toward the isolation of the EPMR gene.