RT Journal Article SR Electronic T1 Novel GABRG2 mutations cause familial febrile seizures JF Neurology Genetics JO Neurol Genet FD Lippincott Williams & Wilkins SP e35 DO 10.1212/NXG.0000000000000035 VO 1 IS 4 A1 Boillot, Morgane A1 Morin-Brureau, Mélanie A1 Picard, Fabienne A1 Weckhuysen, Sarah A1 Lambrecq, Virginie A1 Minetti, Carlo A1 Striano, Pasquale A1 Zara, Federico A1 Iacomino, Michele A1 Ishida, Saeko A1 An-Gourfinkel, Isabelle A1 Daniau, Mailys A1 Hardies, Katia A1 Baulac, Michel A1 Dulac, Olivier A1 Leguern, Eric A1 Nabbout, Rima A1 Baulac, Stéphanie YR 2015 UL http://ng.neurology.org/content/1/4/e35.abstract 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