FGD6 EXPRESSION IN FOCAL BENIGN INFANTILE EPILEPSY (FBIE): ITS POTENTIAL ROLE IN EPILEPSY PATHOPHYSIOLOGY

GALVÁN DANIELA INÉS; CASABONA JUAN CRUZ; KOCHEN S; GARCÍA CORINA ILEANA; CASALÍA MARIANA; GONZALEZ JOAQUÍN; PITOSSI FERNANDO JUAN; FARÍAS MARÍA ISABEL; CAVALIERE CANDEDO VERÓNICA; KAUFFMAN MARCELO

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Epilepsy is the third most common cause of neurological disorders. FocalBenign Infantile Epilepsy (FBIE) is the most prevalent in the paediatricpopulation and belongs to the idiopathic epilepsy group. A recent geneticanalysis of familial FBIE determined FGD6 as a potential candidate to beinvolved in epilepsy pathogenesis. The affected members presented ap.E276G mutation in homozygosis, suggesting mutated FGD6 as a probablecause of epilepsy in this family. FGD6 function is not well established. Itbelongs to FGD family, in which some of the members have a known functionsuch as Cdc42 GEF (guanine exchange factors) activators. Cdc42 is a RhoGTPase and has a key role in CNS, regulating cytoskeleton, synaptogenesis,spines and dendrite formation and axon guidance. We studied FGD6expression in several culture models using, wild type, FGD6 heterozygous andFGD6 homozygous cells. Our results show that in a neuroepithelial culturemodel with induced pluripotent cells (IPS), FGD6 is expressed in neurons in thethree experimental groups. In this model, FGD6 is found aggregated in thecytoplasm and plasma membrane when analysed cells from epileptic subjectswith a homozygous mutation in FGD6, compared to a homogeneousdistribution in wild type cells. Cytoskeleton studies in fibroblasts revealed adecrease in actin filaments, as well as disorganization of the cytoskeleton inepileptic patients. Finally, we studied by qRT-PCR FGD6 expression in a SK-N-SH neuroblastoma cells, and we observed a decrease in gene expressionwhen the cells differentiate to a more mature phenotype (p≤0,05), followed by araise in FGD6 mRNA as the cells continue to differentiate. Our results suggestthat in neurons FGD6 expression is tightly regulated during cell maturation, andthat FGD6 mutation affects cytoskeleton dynamics.