The Gene for a Recessively Inherited Human Childhood Progressive Epilepsy with Mental Retardation Maps to the Distal Short Arm of Chromosome 8

• Published in: Proceedings of the National Academy of Sciences - PNAS 1994-07, Vol.91 (15), p.7267-7270
• Main Authors: Tahvanainen, Esa, Ranta, Susanna, Hirvasniemi, Aune, Karila, Elvi, Leisti, Jaakko, Sistonen, Pertti, Weissenbach, Jean, Lehesjoki, Anna-Elina, dela Chapelle, Albert
• Format: Article
• Language: English
• Subjects: Adult; Age of Onset; Alleles; Child; Child, Preschool; Children & youth; chromosome 8; Chromosome Mapping; Chromosomes; Chromosomes, Human, Pair 8; Epilepsy; Epilepsy - complications; Epilepsy - genetics; gene mapping; Genes; Genes, Recessive; Genetic diseases; Genetic Linkage; Genetic loci; Genetic Markers; Genetic mutation; Genetics; Haplotypes; Humans; Intellectual Disability - complications; Intellectual Disability - genetics; man; Mental retardation; Middle Aged; Mutation; Phenotype; Phenotypes; Seizures; Telomere
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.91.15.7267

A recently delineated childhood epilepsy has hitherto been observed only in a small geographic region in northern Finland, where, with the exception of one, both parents of all of the 11 sibships with affected individuals descend from one or two founding couples. The disease is characterized by generalized tonic-clonic seizures with onset at 5-10 years and progressive, severe mental retardation with onset 2-5 years after the first seizures. In this study the gene locus is assigned to the telomeric region of chromosome 8p by linkage. Analyses of recombinations 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 at the above five loci support the hypothesis of a single founding mutation for all affected chromosomes except the one belonging to the unrelated parent, who has a very different haplotype, suggesting another mutation 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.