Allelic association of a truncation mutation of the KCNMB3 gene with idiopathic generalized epilepsy

• Published in: American journal of medical genetics. Part B, Neuropsychiatric genetics Vol. 144B; no. 1; pp. 10 - 13
• Main Authors: Lorenz, Susanne, Heils, Armin, Kasper, Johannes M., Sander, Thomas
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 05.01.2007; Wiley-Liss
• Subjects: absence epilepsy; Alleles; association; Base Sequence; Biological and medical sciences; Case-Control Studies; DNA - genetics; Epilepsies, Myoclonic - genetics; Epilepsies, Myoclonic - metabolism; Epilepsy, Absence - genetics; Epilepsy, Absence - metabolism; Epilepsy, Generalized - genetics; Epilepsy, Generalized - metabolism; Exons; Gene Frequency; genetics; Genotype; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Humans; idiopathic generalized epilepsy; KCNMB3; Large-Conductance Calcium-Activated Potassium Channel beta Subunits - genetics; Medical genetics; Medical sciences; Nerve Tissue Proteins - genetics; Nervous system (semeiology, syndromes); Neurology; Sequence Deletion; idiopathic generalized epilepsy; absence epilepsy; Nervous system diseases; Epilepsy; Idiopathic; Cerebral disorder; Truncation; Association; Gene; Central nervous system disease; KCNMB3; Genetics; Mutation
• ISSN: 1552-4841; 1552-485X
• DOI: 10.1002/ajmg.b.30369

The gene encoding the β3‐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 β3b‐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 β3b‐truncation confers a common epileptogenic effect preferentially to the ictogenesis of typical absence seizures. © 2006 Wiley‐Liss, Inc.