title: Phenotypic spectrum of GABRA1: From generalized epilepsies to severe epileptic encephalopathies.
abstract: To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations.
  
  
  
  Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analysis of 4 selected mutations was performed using the Xenopus laevis oocyte expression system.
  
  
  
  The study included 16 novel probands and 3 additional family members with a disease-causing mutation in the GABRA1 gene. The phenotypic spectrum varied from unspecified epilepsy (1), juvenile myoclonic epilepsy (2), photosensitive idiopathic generalized epilepsy (1), and generalized epilepsy with febrile seizures plus (1) to severe epileptic encephalopathies (11). In the epileptic encephalopathy group, the patients had seizures beginning between the first day of life and 15 months, with a mean of 7 months. Predominant seizure types in all patients were tonic-clonic in 9 participants (56%) and myoclonic seizures in 5 (31%). EEG showed a generalized photoparoxysmal response in 6 patients (37%). Four selected mutations studied functionally revealed a loss of function, without a clear genotype-phenotype correlation.
  
  
  
  GABRA1 mutations make a significant contribution to the genetic etiology of both benign and severe epilepsy syndromes. Myoclonic and tonic-clonic seizures with pathologic response to photic stimulation are common and shared features in both mild and severe phenotypes.
authors: Authors' affiliations are listed at the end of the article.
authors: Katrine
authors: K
authors: Johannesen
authors: Authors' affiliations are listed at the end of the article.
authors: Carla
authors: C
authors: Marini
authors: Authors' affiliations are listed at the end of the article.
authors: Siona
authors: S
authors: Pfeffer
authors: Authors' affiliations are listed at the end of the article.
authors: Rikke S
authors: RS
authors: Møller
authors: Authors' affiliations are listed at the end of the article.
authors: Thomas
authors: T
authors: Dorn
authors: Authors' affiliations are listed at the end of the article.
authors: Cristina Elena
authors: CE
authors: Niturad
authors: Authors' affiliations are listed at the end of the article.
authors: Elena
authors: E
authors: Gardella
authors: Authors' affiliations are listed at the end of the article.
authors: Yvonne
authors: Y
authors: Weber
authors: Authors' affiliations are listed at the end of the article.
authors: Marianne
authors: M
authors: Søndergård
authors: Authors' affiliations are listed at the end of the article.
authors: Helle
authors: H
authors: Hjalgrim
authors: Authors' affiliations are listed at the end of the article.
authors: Mariana
authors: M
authors: Nikanorova
authors: Authors' affiliations are listed at the end of the article.
authors: Felicitas
authors: F
authors: Becker
authors: Authors' affiliations are listed at the end of the article.
authors: Line H G
authors: LH
authors: Larsen
authors: Authors' affiliations are listed at the end of the article.
authors: Hans A
authors: HA
authors: Dahl
authors: Authors' affiliations are listed at the end of the article.
authors: Oliver
authors: O
authors: Maier
authors: Authors' affiliations are listed at the end of the article.
authors: Davide
authors: D
authors: Mei
authors: Authors' affiliations are listed at the end of the article.
authors: Saskia
authors: S
authors: Biskup
authors: Authors' affiliations are listed at the end of the article.
authors: Karl M
authors: KM
authors: Klein
authors: Authors' affiliations are listed at the end of the article.
authors: Philipp S
authors: PS
authors: Reif
authors: Authors' affiliations are listed at the end of the article.
authors: Felix
authors: F
authors: Rosenow
authors: Authors' affiliations are listed at the end of the article.
authors: Abdallah F
authors: AF
authors: Elias
authors: Authors' affiliations are listed at the end of the article.
authors: Cindy
authors: C
authors: Hudson
authors: Authors' affiliations are listed at the end of the article.
authors: Katherine L
authors: KL
authors: Helbig
authors: Authors' affiliations are listed at the end of the article.
authors: Susanne
authors: S
authors: Schubert-Bast
authors: Authors' affiliations are listed at the end of the article.
authors: Maria R
authors: MR
authors: Scordo
authors: Authors' affiliations are listed at the end of the article.
authors: Dana
authors: D
authors: Craiu
authors: Authors' affiliations are listed at the end of the article.
authors: Tania
authors: T
authors: Djémié
authors: Authors' affiliations are listed at the end of the article.
authors: Dorota
authors: D
authors: Hoffman-Zacharska
authors: Authors' affiliations are listed at the end of the article.
authors: Hande
authors: H
authors: Caglayan
authors: Authors' affiliations are listed at the end of the article.
authors: Ingo
authors: I
authors: Helbig
authors: Authors' affiliations are listed at the end of the article.
authors: Jose
authors: J
authors: Serratosa
authors: Authors' affiliations are listed at the end of the article.
authors: Pasquale
authors: P
authors: Striano
authors: Authors' affiliations are listed at the end of the article.
authors: Peter
authors: P
authors: De Jonghe
authors: Authors' affiliations are listed at the end of the article.
authors: Sarah
authors: S
authors: Weckhuysen
authors: Authors' affiliations are listed at the end of the article.
authors: Arvid
authors: A
authors: Suls
authors: Authors' affiliations are listed at the end of the article.
authors: Kai
authors: K
authors: Muru
authors: Authors' affiliations are listed at the end of the article.
authors: Inga
authors: I
authors: Talvik
authors: Authors' affiliations are listed at the end of the article.
authors: Tiina
authors: T
authors: Talvik
authors: Authors' affiliations are listed at the end of the article.
authors: Hiltrud
authors: H
authors: Muhle
authors: Authors' affiliations are listed at the end of the article.
authors: Ingo
authors: I
authors: Borggraefe
authors: Authors' affiliations are listed at the end of the article.
authors: Imma
authors: I
authors: Rost
authors: Authors' affiliations are listed at the end of the article.
authors: Renzo
authors: R
authors: Guerrini
authors: Authors' affiliations are listed at the end of the article.
authors: Holger
authors: H
authors: Lerche
authors: Authors' affiliations are listed at the end of the article. johannes.lemke@medizin.uni-leipzig.de guru@filadelfia.dk.
authors: Johannes R
authors: JR
authors: Lemke
authors: Authors' affiliations are listed at the end of the article. johannes.lemke@medizin.uni-leipzig.de guru@filadelfia.dk.
authors: Guido
authors: G
authors: Rubboli
authors: Authors' affiliations are listed at the end of the article.
authors: Snezana
authors: S
authors: Maljevic
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001921:Brain / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008875:Middle Aged; D009154:Mutation; D009865:Oocytes; D010641:Phenotype; D011963:Receptors, GABA-A / Q000235:genetics* / Q000378:metabolism; D014982:Xenopus laevis; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C546240:GABRA1 protein, human; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid