A multidisciplinary approach is being taken utilizing the expertise of clinicians, geneticists, and molecular biologists for this translational research. This project proposes to collect blood samples from patients with common forms of epilepsy (1500 persons) and their parents (3000 persons) over the course of five years. DNA will be extracted from these blood samples and specific genes will be studied for evidence of mutation related to seizure susceptibility. Results from these linkage data demonstrate that an epilepsy susceptibility gene is located on mouse chromosome 1 (Chr.1), and by conserved synteny, human Chr. 1. We identified a variation in a potassium ion channel gene that may represent the seizure susceptibility locus in our animal model. Preliminary data in humans confirms the existence of a variation in the same gene that is associated with seizure disorder. Further genetic analyses will be used to characterize the extent of association between specific gene variation and illness. This will be accomplished by measuring the passage of variations from parents to ill children and searching for those that are inherited by ill children more often than predicted statistically based on classical genetics. We have the ability to identify, ascertain ana analyze DNA samples from hundreds of individuals for these proposed studies. At minimum the identification of epilepsy susceptibility genes will focus further research on distinct mechanisms of seizure initiation and/or propagation. Additionally, identified gene variations will provide molecular markers for use in combination with EEG data for more accurate diagnosis in epilepsy patients. Finally, identification of seizure susceptibility alleles will provide molecular targets for new anticonvulsant drug design.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS040396-03
Application #
6613810
Study Section
Mammalian Genetics Study Section (MGN)
Program Officer
Fureman, Brandy E
Project Start
2001-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
3
Fiscal Year
2003
Total Cost
$491,511
Indirect Cost
Name
University of Pennsylvania
Department
Psychiatry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Nurmohamed, Laila; Garcia-Bournissen, Facundo; Buono, Russell J et al. (2010) Predisposition to epilepsy--does the ABCB1 gene play a role? Epilepsia 51:1882-5
Tracy, J I; Dechant, V; Sperling, M R et al. (2007) The association of mood with quality of life ratings in epilepsy. Neurology 68:1101-7
Lohoff, Falk W; Ferraro, Thomas N; Dahl, John P et al. (2005) Lack of association between variations in the brain-derived neurotrophic factor (BDNF) gene and temporal lobe epilepsy. Epilepsy Res 66:59-62
Lohoff, Falk W; Ferraro, Thomas N; Sander, Thomas et al. (2005) No association between common variations in the human alpha 2 subunit gene (ATP1A2) of the sodium-potassium-transporting ATPase and idiopathic generalized epilepsy. Neurosci Lett 382:33-8
Khoury, John S; Winokur, Ronald S; Tracy, Joseph I et al. (2005) Predicting seizure frequency after epilepsy surgery. Epilepsy Res 67:89-99
Buono, R J; Lohoff, F W; Sander, T et al. (2004) Association between variation in the human KCNJ10 potassium ion channel gene and seizure susceptibility. Epilepsy Res 58:175-83