title: Sequencing of the GRIK1 gene in patients with juvenile absence epilepsy does not reveal mutations affecting receptor structure.
abstract: Hereditary factors play a major role in the etiology of juvenile absence epilepsy (JAE) that is a common subtype of idiopathic generalized epilepsy (IGE). Sander et al. [1997: Am J Med Genet 74:416-421] reported an allelic association of JAE with the nine-copy allele of a tetranucleotide repeat polymorphism in the third intron of the kainate-selective GluR5 receptor gene (GRIK1) and supportive evidence for linkage of IGE to GRIK1 in families of JAE probands. These findings suggest that a major genetic determinant of GRIK1 confers susceptibility to JAE. Assuming that the GRIK1 tetranucleotide repeat polymorphism is unlikely to have functional relevance itself, we have sequenced the coding regions and regulatory sequences of the GRIK1 gene in eight JAE patients who carry the nine-repeat allele of the GRIK1 tetranucleotide repeat polymorphism to detect a putative functional GRIK1 mutation that is in linkage disequilibrium with the nine-repeat allele. Seven of them were derived from families showing positive evidence for linkage to GRIK1. Our mutation analysis of coding regions and splice junctions revealed only two silent polymorphisms (A522C and C1173T) out of the five SNPs present in public databases and no mutations affecting protein structure. No significant differences were found in the allele frequencies of the detected polymorphisms between the JAE patients and controls. High levels of sequence conservation were also found in the promoter, in the 5' and both the 3' untranslated regions and in the RNA secondary structure involved in the editing reaction. The results presented indicate that mutations in the coding sequences, in the intron-exon boundaries and in the main regulatory regions of the GRIK1 are not commonly involved in the etiology of JAE.
authors.affiliation: Division of Biology and Genetics, Department of Biomedical Sciences and Biotechnologies, Brescia University Medical School, Brescia, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Izzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Barbon
authors.forename: Rebekka
authors.initials: R
authors.lastname: Kretz
authors.forename: Thomas
authors.initials: T
authors.lastname: Sander
authors.forename: Sergio
authors.initials: S
authors.lastname: Barlati
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D001483:Base Sequence; D002648:Child; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004832:Epilepsy, Absence / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018092:Kainic Acid Receptors / Q000235:genetics*
chemical_list: D004247:DNA; D018092:Kainic Acid Receptors