Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy

Nat Genet. 2002 Jun;31(2):184-9. doi: 10.1038/ng885. Epub 2002 May 6.


Although many genes that predispose for epilepsy in humans have been determined, those that underlie the classical syndromes of idiopathic generalized epilepsy (IGE) have yet to be identified. We report that an Ala322Asp mutation in GABRA1, encoding the alpha1 subunit of the gamma-aminobutyric acid receptor subtype A (GABA(A)), is found in affected individuals of a large French Canadian family with juvenile myoclonic epilepsy. Compared with wildtype receptors, GABA(A) receptors that contain the mutant subunit show a lesser amplitude of GABA-activated currents in vitro, indicating that seizures may result from loss of function of this inhibitory ligand-gated channel. Our results confirm that mutation of GABRA1 predisposes towards a common idiopathic generalized epilepsy syndrome in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Amino Acid Sequence
  • Amino Acid Substitution / genetics
  • Child
  • Child, Preschool
  • Epilepsy, Generalized / etiology
  • Epilepsy, Generalized / genetics
  • Genes, Dominant
  • Genetic Predisposition to Disease
  • Humans
  • Molecular Sequence Data
  • Mutation, Missense* / genetics
  • Myoclonic Epilepsy, Juvenile / etiology
  • Myoclonic Epilepsy, Juvenile / genetics*
  • Pedigree
  • Receptors, GABA-A / genetics*


  • Receptors, GABA-A

Associated data

  • GENBANK/A27142
  • GENBANK/P19150
  • RefSeq/NM_000806