Exclusion of the JRK/JH8 gene as a candidate for human childhood absence epilepsy mapped on 8q24

Childhood absence epilepsy (CAE), one of the most common epilepsies in chil dren, is genetically and phenotypically heterogeneous. One of the genes res ponsible for human CAE associated with tonic-clonic seizures has been mappe d to chromosome band 8q24 by genetic linkage analysis and is termed ECA1. R ecently, we isolated and mapped the JRK/JH8 gene, a human homologue of the mouse epilepsy gene, jerky, on 8q24. The epilepsy phenotype of the mice wit h inactivated jerky gene as well as its chromosomal localization proposed J RK/JH8 as a prominent candidate for the CAE gene. To confirm whether the JR K/JH8 gene is responsible for ECA1, we performed mutational analyses in the coding region of JRK/JH8 in two CAE families mapped on 8q24, using heterod uplex and direct sequencing methods. We identified seven nucleotide changes , two of which lead to amino acid substitutions. However, these changes did not co-segregate with the disease phenotype. In addition, we redefined the location of JRK/JH8 to be more than 4 Mb distant from D8S502 and ECA1. Thu s, negative results of mutation analyses and detailed physical mapping excl ude JRK/JH8 as the ECA1 gene. (C) 1999 Elsevier Science B.V. All rights res erved.