Abstracts

Rationale: Genomic copy number variations (CNVs) have been identified as a risk factors for some forms of epilepsy syndromes. Therefore, we aimed: 1) to investigate the distribution of CNVs in patients with mesial temporal lobe epilepsy (MTLE) and in patients with genetic generalized epilepsy (GGE); 2) to identify genes potentially involved in the genetic predisposition to MTLE and GGE within the regions of CNVs found exclusively in the patients. Methods: The sample was compound by 750 individuals (340 patients with MTLE, 70 patients with GGE and 340 control subjects). CNVs were evaluated using the Affymetrix SNP 6.0 array. Results: We identified 2,246 CNVs in patients with MTLE, 20% of which were found exclusively in patients with MTLE. Some chromosomal regions affected by these CNVs are 1p36.13, 2q24.1, 7q35, 8p23.1, 8q24.23, 10q11.22, 14q23.2, 15q11.2, 15q13.2, 15q14, 16p13.11, 16q22.1, 17q12, 17q21.31, 17q25.3, 19p12. These CNVs affects 652 RefSeq genes. We identified an enrichment of genes associated with neurogenesis development and synaptogenesis, learning or memory, cognition, pre-pulse inhibition, ion transport, protein complex assembly involved in synapse maturation, calcium ion transmembrane transport and single-organism behavior. On the other hand, in patients with GGE, we identified 340 CNVs, 17% of which were found only in patients with GGE. These CNVs affects the following chromosomal regions: 1p36.13, 1q21.1, 1q31.3, 1q32.2, 2p11.2, 3p21.2, 3p26.1, 3p14.2, 4q28.3, 16q22.2, 20p12.1 and involve 59 RefSeq genes. There was an enrichment of genes associated with lithium effect on synaptic transmission and autophagy, glutamic acid regulation of dopamine D1A receptor signaling, mitochondrial dysfunction in neurodegenerative diseases, dopamine D2 receptor transactivation of PDGFR in CNS, GABA-B receptor-mediated regulation of glutamate signaling in Purkinje cells, nicotine signaling in dopaminergic neurons and dopamine D2 receptor signaling in CNS.  Conclusions: Our results show that there are CNVs in specific chromosomal regions of the genome in patients with epilepsy. These regions are distinct in patients with MTLE as compared to patients with GGE. These CNVs affect genes in several important biology pathways. Funding: Support: FAPESP, CNPq.