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