The Experience Of The GENESS International Consortium To Accelerate Discovery Of New Epilepsy Genes (P3.007)

OBJECTIVE: To describe the experience of the GENESS international consortium to accelerate discovery of genes causing juvenile myoclonic epilepsy (JME) and childhood absence epilepsy (CAE). BACKGROUND: The GENESS physicians and researchers from the USA, Latin America, Japan, Spain, Italy and Belgium collaborate to find more genes for epilepsies and to study their function as first step to finding repairs and cures. This collaboration discovered mutations of genes for JME in chromosome 6p11 (EFHC1), CAE in 15q12 (GABRB3) and Progressive Myoclonus Epilepsy of Lafora in 6q24 (Laforin/DSP). Currently new epilepsy loci and genes are being confirmed. DESIGN/METHODS: Since 1992, the participating study sites follow the same protocol and intake form for enrollment, collecting demographic, clinical, EEG and imaging data. Validation of diagnoses is done by site visits from the principal investigators and by a remote system with a study coordinator. We use a database especially designed by the consortium, allowing the definition of subsyndromes, stage of disease and follow-up analysis. Functional studies and knockout mice are done in various labs. RESULTS: This collaboration has resulted in the participation of 658 families: 255 (39%) from USA, 311 (47%) from Mexico, 93 (14%) from Honduras, 17 (3%) from Brazil and 12 (2%) from other countries. The distribution by syndromes is as follows: 526 JME families (80%), 93 with absence syndromes 14%, 70 with other syndromes related or yet to classify (11%). To date, 57 additional families are being validated and will be entered in the series. The data has helped us understand the existence of subsyndromes not reported in the literature before, such as CAE evolving to JME. Studies continue to evaluate the frequency of epilepsy mutations and the effect of modifier genes. CONCLUSION: The GENESS consortium has the potential of discovering more epilepsy genes, and at the same time, is a valuable endeavor resulting in technology transfer, capacity building at participating sites, and the training of physicians who help improve epilepsy care. Disclosure: Dr. Escueta has nothing to disclose. Dr. Alonso has nothing to disclose. Dr. Medina has nothing to disclose. Dr. Duron has received personal compensation for activities with Danny Did Foundation. Dr. Bailey has nothing to disclose. Dr. Martinez-Juarez has received personal compensation for activities with Abbott Laboratories, Inc. Dr. Tanaka has nothing to disclose. Dr. Bai has nothing to disclose. Dr. Jara-Prado has nothing to disclose. Dr. Ochoa has nothing to disclose. Dr. Machado-Salas has nothing to disclose. Dr. Grisar has nothing to disclose. Dr. Yamakawa has nothing to disclose. Dr. Targas Yacubian has received personal compensation for activities with Johnson & Johnson as a scientific advisory board member, and with Novartis and Abbott Laboratories as a speaker. Dr. Guilhoto has nothing to disclose. Dr. Serratosa has received personal compensation for activities with Eisai Inc., UCB Pharma, and Bial. Dr. Patterson has nothing to disclose. Dr. Spellman has nothing to disclose. Dr. Wight has nothing to disclose. Dr. Lin has nothing to disclose. Dr. Aftab has nothing to disclose.