title: Polymorphism analysis of JRK/JH8, the human homologue of mouse jerky, and description of a rare mutation in a case of CAE evolving to JME.
abstract: Disruption of the function of the mouse jerky gene by transgene insertion causes generalized recurrent seizures reminiscent of human idiopathic generalized epilepsy (IGE). A human homologue, JRK/JH8, has been cloned, which maps to 8q24, a chromosomal region associated with several forms of IGE. JRK/JH8 is, therefore, a candidate locus for at least some forms of IGE. We report corrected cDNA sequences and extended open reading frames for the mouse jerky and human JRK/JH8 genes, which add 48 amino acids to the N-terminus of the Jerky protein and which extends the region of homology with the N-terminal DNA-binding domain of the centromere-binding protein, CENP-B. Systematic sequencing of the coding region of the extended JRK/JH8 gene identified single nucleotide polymorphisms that define three haplotypes, which were used for association studies in patients with idiopathic generalized epilepsy. We report one subject with childhood absence epilepsy (CAE) that evolved to juvenile myoclonic epilepsy (JME) that has a unique de novo mutation that results in a non-conservative amino acid change at a potential protein glycosylation site. Familial analysis supports a causal role for this mutation in the disease.
authors.affiliation: Department of Biochemistry, University College Cork, Lee Maltings, Prospect Row, Cork, Ireland. t.moore@ucc.ie
authors.forename: T
authors.initials: T
authors.lastname: Moore
authors.forename: S
authors.initials: S
authors.lastname: Hecquet
authors.forename: A
authors.initials: A
authors.lastname: McLellann
authors.forename: D
authors.initials: D
authors.lastname: Ville
authors.forename: D
authors.initials: D
authors.lastname: Grid
authors.forename: F
authors.initials: F
authors.lastname: Picard
authors.forename: B
authors.initials: B
authors.lastname: Moulard
authors.forename: P
authors.initials: P
authors.lastname: Asherson
authors.forename: A J
authors.initials: AJ
authors.lastname: Makoff
authors.forename: D
authors.initials: D
authors.lastname: McCormick
authors.forename: L
authors.initials: L
authors.lastname: Nashef
authors.forename: P
authors.initials: P
authors.lastname: Froguel
authors.forename: A
authors.initials: A
authors.lastname: Arzimanoglou
authors.forename: E
authors.initials: E
authors.lastname: LeGuern
authors.forename: B
authors.initials: B
authors.lastname: Bailleul
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D004832:Epilepsy, Absence / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D020190:Myoclonic Epilepsy, Juvenile / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D016366:Open Reading Frames / Q000235:genetics; D010375:Pedigree; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins; D012016:Reference Values
chemical_list: D004268:DNA-Binding Proteins; C113872:JRK protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; C095835:jrk protein, mouse