title: Allelic association of a truncation mutation of the KCNMB3 gene with idiopathic generalized epilepsy.
abstract: The gene encoding the beta3-subunit regulatory subunit (KCNMB3) of large conductance calcium-sensitive potassium (BK) channels represents a positional and functional candidate gene for idiopathic generalized epilepsy (IGE). A single base pair deletion in exon 4 of KCNMB3 (delA750) alters/truncates the terminal 21 amino acids of the 3-subunit and affects channel inactivation of the beta3b-isoform. The present association study tested whether the KCNMB3 delA750 mutation confers susceptibility to common IGE syndromes. In total, 592 unrelated German IGE patients and 462 healthy population controls were genotyped for the delA750 truncation mutation. The frequency of the delA750 mutation was significantly increased in the IGE patients (7.9%) compared to that in the controls (5.5%; P = 0.016, one-sided; OR = 1.52; 95%-CI: 1.05-2.21). The increase of the delA750 frequency was accentuated in 312 patients exhibiting typical absence seizures (8.8%, P = 0.005, one-sided; OR = 1.72; 95%-CI: 1.13-2.62) relatively to that observed in the 237 patients with myoclonic seizures on awakening (7.2%; P = 0.11, one-sided; OR = 1.36; 95%-CI: 0.85-2.19), when compared with controls. The present results suggest that the functional KCNMB3 beta3b-truncation confers a common epileptogenic effect preferentially to the ictogenesis of typical absence seizures.
authors.affiliation: Gene Mapping Center, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Lorenz
authors.forename: Armin
authors.initials: A
authors.lastname: Heils
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Kasper
authors.forename: Thomas
authors.initials: T
authors.lastname: Sander
mesh_terms: D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D004831:Epilepsies, Myoclonic / Q000235:genetics / Q000378:metabolism; D004832:Epilepsy, Absence / Q000235:genetics / Q000378:metabolism; D004829:Epilepsy, Generalized / Q000235:genetics* / Q000378:metabolism; D005091:Exons; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: C403242:KCNMB3 protein, human; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D009419:Nerve Tissue Proteins; D004247:DNA