Details

Autor(en) / Beteiligte

• Boillot, Morgane
• Morin-Brureau, Mélanie
• Picard, Fabienne
• Weckhuysen, Sarah
• Lambrecq, Virginie
• Minetti, Carlo
• Striano, Pasquale
• Zara, Federico
• Iacomino, Michele
• Ishida, Saeko
• An-Gourfinkel, Isabelle
• Daniau, Mailys
• Hardies, Katia
• Baulac, Michel
• Dulac, Olivier
• Leguern, Eric
• Nabbout, Rima
• Baulac, Stéphanie

Titel

Novel GABRG2 mutations cause familial febrile seizures

Ist Teil von

• Neurology. Genetics, 2015-12, Vol.1 (4), p.e35-e35

Ort / Verlag

United States: American Academy of Neurology

Erscheinungsjahr

2015

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• 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. 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. 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. 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.