TY - JOUR T1 - Disruption of <em>Fgf13</em> Causes Synaptic Excitatory–Inhibitory Imbalance and Genetic Epilepsy and Febrile Seizures Plus JF - The Journal of Neuroscience JO - J. Neurosci. SP - 8866 LP - 8881 DO - 10.1523/JNEUROSCI.3470-14.2015 VL - 35 IS - 23 AU - Ram S. Puranam AU - Xiao Ping He AU - Lijun Yao AU - Tri Le AU - Wonjo Jang AU - Catherine W. Rehder AU - Darrell V. Lewis AU - James O. McNamara Y1 - 2015/06/10 UR - http://www.jneurosci.org/content/35/23/8866.abstract N2 - We identified a family in which a translocation between chromosomes X and 14 was associated with cognitive impairment and a complex genetic disorder termed “Genetic Epilepsy and Febrile Seizures Plus” (GEFS+). We demonstrate that the breakpoint on the X chromosome disrupted a gene that encodes an auxiliary protein of voltage-gated Na+ channels, fibroblast growth factor 13 (Fgf13). Female mice in which one Fgf13 allele was deleted exhibited hyperthermia-induced seizures and epilepsy. Anatomic studies revealed expression of Fgf13 mRNA in both excitatory and inhibitory neurons of hippocampus. Electrophysiological recordings revealed decreased inhibitory and increased excitatory synaptic inputs in hippocampal neurons of Fgf13 mutants. We speculate that reduced expression of Fgf13 impairs excitability of inhibitory interneurons, resulting in enhanced excitability within local circuits of hippocampus and the clinical phenotype of epilepsy. These findings reveal a novel cause of this syndrome and underscore the powerful role of FGF13 in control of neuronal excitability. ER -