PT - JOURNAL ARTICLE AU - Boillot, Morgane AU - Morin-Brureau, Mélanie AU - Picard, Fabienne AU - Weckhuysen, Sarah AU - Lambrecq, Virginie AU - Minetti, Carlo AU - Striano, Pasquale AU - Zara, Federico AU - Iacomino, Michele AU - Ishida, Saeko AU - An-Gourfinkel, Isabelle AU - Daniau, Mailys AU - Hardies, Katia AU - Baulac, Michel AU - Dulac, Olivier AU - Leguern, Eric AU - Nabbout, Rima AU - Baulac, Stéphanie TI - Novel <em>GABRG2</em> mutations cause familial febrile seizures AID - 10.1212/NXG.0000000000000035 DP - 2015 Dec 01 TA - Neurology Genetics PG - e35 VI - 1 IP - 4 4099 - http://ng.neurology.org/content/1/4/e35.short 4100 - http://ng.neurology.org/content/1/4/e35.full SO - Neurol Genet2015 Dec 01; 1 AB - Objective: To identify the genetic cause in a large family with febrile seizures (FS) and temporal lobe epilepsy (TLE) and subsequently search for additional mutations in a cohort of 107 families with FS, with or without epilepsy.Methods: The cohort consisted of 1 large family with FS and TLE, 64 smaller French families recruited through a national French campaign, and 43 Italian families. Molecular analyses consisted of whole-exome sequencing and mutational screening.Results: Exome sequencing revealed a p.Glu402fs*3 mutation in the γ2 subunit of the GABAA receptor gene (GABRG2) in the large family with FS and TLE. Three additional nonsense and frameshift GABRG2 mutations (p.Arg136*, p.Val462fs*33, and p.Pro59fs*12), 1 missense mutation (p.Met199Val), and 1 exonic deletion were subsequently identified in 5 families of the follow-up cohort.Conclusions: We report GABRG2 mutations in 5.6% (6/108) of families with FS, with or without associated epilepsy. This study provides evidence that GABRG2 mutations are linked to the FS phenotype, rather than epilepsy, and that loss-of-function of GABAA receptor γ2 subunit is the probable underlying pathogenic mechanism.FS=febrile seizures; GEFS+=genetic epilepsy with febrile seizures plus; GTCS=generalized tonic-clonic seizures; NMD=nonsense-mediated-decay system; TCS=tonic-clonic seizures; TLE=temporal lobe epilepsy