Mutations of [italic]CLCN2[/italic], Encoding a Voltage-Gated Chloride Channel, Causing Common Forms of Epilepsy.
Abstract number :
1.061
Submission category :
Year :
2001
Submission ID :
2704
Source :
www.aesnet.org
Presentation date :
12/1/2001 12:00:00 AM
Published date :
Dec 1, 2001, 06:00 AM
Authors :
A.B. Heils, MD, Epileptology, University of Bonn, Bonn, Germany; K. Haug, MD, Human Genetics, University of Bonn, Bonn, Germany; T. Sander, MD, Neurology, University Hospital Charite, Berlin, Germany; P.L. Cid, PhD, Centro de Estudios Cientificos, Valdivi
RATIONALE: To identify genes, which confer susceptibility to common and genetically complex forms of idiopathic generalized epilepsy (IGE).
METHODS: Based on the results of a recent genome-wide linkage study in common IGE subtypes (T. Sander et al.,2000) we followed a positional candidate gene approach. We systematically searched for mutations and common sequence variation in [italic]CLCN2[/italic]. One mutation was transcfected into HEK 293 cells and investigated by the whole cell patch clamp technique. A common sequence variation was further investigated in a family-based association study.
RESULTS: We identified three rare mutations, which cosegregate with the IGE trait in three extended IGE families. One of these mutations, a non-conservative G to E exchange, leads to a significantly slower current in response to moderate neagtive voltages. A novel common polymorphism is significantly associated with IGE and confers susceptibility to broad spectrum of IGE.
CONCLUSIONS: [italic]CLCN2[/italic] is the first gene, in which both rare mutations and a common sequence variation confer a range of varying susceptibility effects to genetically complex epilepsies.
Support: The German Volkswagen-Stiftung, The Deutsche Forschungsgemeinschaft, The German Genomic Networks (BMBF).