BRD2 (RING3) is a probable major susceptibility gene for common juvenile myoclonic epilepsy

Am J Hum Genet. 2003 Aug;73(2):261-70. doi: 10.1086/377006. Epub 2003 Jun 25.


Juvenile myoclonic epilepsy (JME) is a common form of generalized epilepsy that starts in adolescence. A major JME susceptibility locus (EJM1) was mapped to chromosomal region 6p21 in three independent linkage studies, and association was reported between JME and a microsatellite marker in the 6p21 region. The critical region for EJM1 is delimited by obligate recombinants at HLA-DQ and HLA-DP. In the present study, we found highly significant linkage disequilibrium (LD) between JME and a core haplotype of five single-nucleotide-polymorphism (SNP) and microsatellite markers in this critical region, with LD peaking in the BRD2 (RING3) gene (odds ratio 6.45; 95% confidence interval 2.36-17.58). DNA sequencing revealed two JME-associated SNP variants in the BRD2 (RING3) promoter region but no other potentially causative coding mutations in 20 probands from families with positive LOD scores. BRD2 (RING3) is a putative nuclear transcriptional regulator from a family of genes that are expressed during development. Our findings strongly suggest that BRD2 (RING3) is EJM1, the first gene identified for a common idiopathic epilepsy. These findings also suggest that abnormalities of neural development may be a cause of common idiopathic epilepsy, and the findings have implications for the generalizability of proposed pathogenetic mechanisms, derived from diseases that show Mendelian transmission, to their complex counterparts.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Case-Control Studies
  • Chromosome Mapping
  • Chromosomes, Human, Pair 6 / genetics
  • DNA Mutational Analysis
  • Female
  • Genetic Variation
  • Humans
  • Linkage Disequilibrium
  • Male
  • Molecular Sequence Data
  • Myoclonic Epilepsy, Juvenile / genetics*
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic
  • Protein Serine-Threonine Kinases / genetics*
  • Transcription Factors


  • BRD2 protein, human
  • Transcription Factors
  • Protein Serine-Threonine Kinases

Associated data

  • RefSeq/NM_005104