title: Linkage analysis between childhood absence epilepsy and genes encoding GABAA and GABAB receptors, voltage-dependent calcium channels, and the ECA1 region on chromosome 8q.
abstract: Childhood absence epilepsy (CAE) is an idiopathic generalised epilepsy (IGE) characterised by onset of typical absence seizures in otherwise normal children of school age. A genetic component to aetiology is well established but the mechanism of inheritance and the genes involved are unknown. Available evidence suggests that mutations in genes encoding GABA receptors or brain expressed voltage-dependent calcium channels (VDCCs) may underlie CAE. The aim of this work was to test this hypothesis by linkage analysis using microsatellite loci spanning theses genes in 33 nuclear families each with two or more individuals with CAE. Seventeen VDCC subunit genes, ten GABA(A)R subunit genes, two GABA(B) receptor genes and the ECA1 locus on 8q24 were investigated using 35 microsatellite loci. Assuming locus homogeneity, all loci gave statistically significant negative LOD scores, excluding these genes as major loci in the majority of these families. Positive HLOD scores assuming locus heterogeneity were observed for CACNG3 on chromosome 16p12-p13.1 and the GABRA5, GABRB3, GABRG3 cluster on chromosome 15q11-q13. Association studies are required to determine whether these loci are the site of susceptibility alleles in a subset of patients with CAE.
authors.affiliation: Department of Paediatrics, Royal Free and University College Medical School, University College London, 5 University Street, WC1E 6JJ, London, UK. robert.robinson@ucl.ac.uk
authors.forename: Robert
authors.initials: R
authors.lastname: Robinson
authors.forename: Nichole
authors.initials: N
authors.lastname: Taske
authors.forename: Thomas
authors.initials: T
authors.lastname: Sander
authors.forename: Armin
authors.initials: A
authors.lastname: Heils
authors.forename: William
authors.initials: W
authors.lastname: Whitehouse
authors.forename: Françoise
authors.initials: F
authors.lastname: Goutières
authors.forename: Jean
authors.initials: J
authors.lastname: Aicardi
authors.forename: Anna Elina
authors.initials: AE
authors.lastname: Lehesjoki
authors.forename: Auli
authors.initials: A
authors.lastname: Siren
authors.forename: Mogens
authors.initials: M
authors.lastname: Laue Friis
authors.forename: Marianne Juel
authors.initials: MJ
authors.lastname: Kjeldsen
authors.forename: Chrysostomos
authors.initials: C
authors.lastname: Panayiotopoulos
authors.forename: Colin
authors.initials: C
authors.lastname: Kennedy
authors.forename: Colin
authors.initials: C
authors.lastname: Ferrie
authors.forename: Michele
authors.initials: M
authors.lastname: Rees
authors.forename: R Mark
authors.initials: RM
authors.lastname: Gardiner
mesh_terms: D015220:Calcium Channels / Q000235:genetics*; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004832:Epilepsy, Absence / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D010375:Pedigree; D011963:Receptors, GABA-A / Q000235:genetics*; D018080:Receptors, GABA-B / Q000235:genetics*
chemical_list: D015220:Calcium Channels; D005819:Genetic Markers; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B