title: Characterization of a 6p21 translocation breakpoint in a family with idiopathic generalized epilepsy.
abstract: The idiopathic generalized epilepsies (IGE), for which a genetic cause is widely accepted, account for 20-30% of all epilepsies. Mapping these epilepsies is difficult, but progress in the positional cloning of idiopathic epilepsy genes responsible for monogenic forms provide emerging evidence that many idiopathic epilepsies are caused by mutations in genes coding for ion channels. Here, we show the characterization of a balanced translocation present in three members of a nuclear family, two of them affected with IGE. The translocation involved chromosome 6p21 [t(4;6) (q35;p21)], a region in which a susceptibility locus for IGE (EJM1) has been reported. Fluorescence in situ hybridization analysis with YACs and PACs resulted in the identification of a PAC clone that included the 6p21 translocation breakpoint. The genomic sequence of this PAC clone contains two 2-pore potassium channel genes, TALK-1 and TALK-2. We characterized the genomic organization of both genes, including three different isoforms of TALK-1, and investigated them in IGE patients, finding some polymorphisms in the coding sequence of TALK-1A.
authors.affiliation: Laboratorio de Neurología, Fundación Jiménez Díaz, Avda. Reyes Católicos 2, Madrid 28040, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Sáez-Hernández
authors.forename: Belén
authors.initials: B
authors.lastname: Peral
authors.forename: Raúl
authors.initials: R
authors.lastname: Sanz
authors.forename: Pilar
authors.initials: P
authors.lastname: Gómez-Garre
authors.forename: Carmen
authors.initials: C
authors.lastname: Ramos
authors.forename: Carmen
authors.initials: C
authors.lastname: Ayuso
authors.forename: José M
authors.initials: JM
authors.lastname: Serratosa
mesh_terms: D000328:Adult; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004829:Epilepsy, Generalized / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D011110:Polymorphism, Genetic / Q000235:genetics; D015221:Potassium Channels / Q000235:genetics; D024683:Potassium Channels, Tandem Pore Domain; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: C477398:KCNK16 protein, human; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D004247:DNA