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.

中文翻译：

---

BRD2（RING3）是常见的青少年肌阵挛性癫痫的可能的主要易感基因。

少年性肌阵挛性癫痫（JME）是普遍性癫痫的一种形式，始于青春期。在三个独立的连锁研究中，一个主要的JME易感性基因座（EJM1）被定位到染色体区域6p21，并且据报道JME与6p21区域中的微卫星标记之间存在关联。EJM1的关键区域由HLA-DQ和HLA-DP上的专职重组体界定。在本研究中，我们发现JME与该关键区域中五个单核苷酸多态性（SNP）和微卫星标记的核心单倍型之间的高度显着连锁不平衡（LD），并且LD在BRD2（RING3）基因中达到峰值（奇数）比率6.45； 95％置信区间2.36-17.58）。DNA测序揭示了BRD2（RING3）启动子区域中的两个JME相关SNP变异，但在LOD得分阳性的20个先证者中没有其他潜在的致病性编码突变。BRD2（RING3）是来自发育过程中表达的基因家族的推定核转录调节因子。我们的发现强烈表明BRD2（RING3）是EJM1，这是鉴定为常见特发性癫痫的第一个基因。这些发现还表明神经发育异常可能是常见的特发性癫痫的原因，并且这些发现对提出的致病机制的普遍性具有潜在意义，所述致病机制是由表现出孟德尔传播的疾病衍生给其复杂的对应物。BRD2（RING3）是来自发育过程中表达的一系列基因的推定核转录调节因子。我们的发现强烈表明BRD2（RING3）是EJM1，这是鉴定为常见特发性癫痫的第一个基因。这些发现还表明神经发育异常可能是常见的特发性癫痫的原因，并且这些发现对提出的致病机制的普遍性具有潜在意义，所述致病机制是由表现出孟德尔传播的疾病衍生给其复杂的对应物。BRD2（RING3）是来自发育过程中表达的基因家族的推定核转录调节因子。我们的发现强烈表明BRD2（RING3）是EJM1，这是鉴定为常见特发性癫痫的第一个基因。这些发现还表明神经发育异常可能是常见的特发性癫痫的原因，并且这些发现对提出的致病机制的普遍性具有潜在意义，所述致病机制是由表现出孟德尔传播的疾病衍生给其复杂的对应物。