MUTATION SCREENING OF THE HUMAN P/Q-TYPE CALCIUM CHANNEL GENE CACNA1A IN COMMON FORMS OF IDIOPATHIC GENERALIZED EPILEPSY
Abstract number :
3.090
Submission category :
Year :
2002
Submission ID :
1839
Source :
www.aesnet.org
Presentation date :
12/7/2002 12:00:00 AM
Published date :
Dec 1, 2002, 06:00 AM
Authors :
Joana Cobilanschi, Johannes Rebstock, Christian E. Elger, Peter Propping, Armin Heils. Institute of Human Genetics, University of Bonn, Bonn, Germany; Clinic of Epileptology, Universityof Bonn, Bonn, Germany
RATIONALE: Several animal models with naturally occurring mutations of the CACNA1A gene exhibit a complex phenotype including spontanous seizures usually accompanied by ataxia. These findings emphasize the human CACNA1A gene as a prime candidate gene in human forms of epilepsy. However, the role of CACNA1A in common forms of idiopathic generalized epilepsy (IGE) remains elusive as no susceptibility mutations have been identified so far.
METHODS: In this study we searched for disease-causing mutations by following a large-scale sequencing approach. We initially included 35 IGE multiplex families with at least two affected siblings. After we excluded linkage to the CACNA1A locus on chromosome 19 in 15 of these families, DNA samples from 20 probands were subjected to automated direct sequencing. We amplified all 47 coding exons and adjacent splice sites.
RESULTS: We found several CACNA1A sequence variants, coding and non-coding, which are currently under investigation with respect to their potential role in the aetiology of common IGE subtypes.
CONCLUSIONS: We conclude that genetic variation in the CACNA1A gene may confer susceptibility to common forms of idiopathic epilepsies in some cases or families, however, the majority of IGE cases must be due to mutations or common sequence variation in genes others than CACNA1A.
[Supported by: Deutsche Volkswagenstiftung and Bundesministerium für Bildung und Forschung (BMBF, NGFN)]