RESOLVING HETEROGENEITY IN EPILEPSY WITH GENETIC MARKERS

青少年肌阵挛性癫痫（JME）或Janz综合征，是一种临床上常见的 一种在青春期开始的良性癫痫 是 以小的肌阵挛性抽搐、阵挛-强直-阵挛-癫痫发作为特征， 特征性EEG特征-4-6 Hz多棘波复合体（4-6 Hz mS&W）。 JME发生在JME患者的亲属中的频率高于 在一般人群中，其他形式的癫痫也是如此。 此外，本发明还提供了一种方法， 4-6 Hz mS&W和其他EEG异常发生在家庭成员中 没有癫痫。 JME是癫痫的一种常见形式，被认为代表了 所有癫痫病患者中的100% 我们最近报道了强有力的证据表明， 在6号染色体上的HLA和BF基因座的亲属中观察到的特征。 的lod 无论假设什么样的继承模式，当我们 将在未受影响的家庭成员中观察到的异常EEG分类为 “受影响” lod评分也保持在3.0以上，无论家庭如何， 患有非JME癫痫的成员被分类。 在最保守的 分类（非JME癫痫被认为是“未受影响”）的lod评分是 4.0以上为隐性遗传。 初步分离分析 表明JME的双位点模型可以被拒绝。 目前的研究旨在确认和进一步调查 JME的遗传学以及JME与其他广义 癫痫 将在纽约的诊所确定JME先证者 区 我们将通过以下方法研究JME和EEG特征的遗传： 连锁标记数据分析以及分离分析。 我们将在五年内收集125个JME家庭的数据。 除了 JmE家庭，我们将收集30个家庭的数据， 1例青少年失神，30例强直阵挛性发作 癫痫发作 这些数据将使我们能够测试JME之间的异质性 和其他形式的癫痫，并测试是否有一个亚组的那些非- JME家族定位于6号染色体。 我们将使用HLA分型和限制 片段长度多态性（RFLP）用于作图，RFLP探针来自 最初来自HLA区域周围。 我们将寻找基因 更接近JME和EEG性状位点的连锁标记。 JME的遗传标记的鉴定给了一个新的焦点， 癫痫的分类和发病机制的基础研究。 的 鉴定参与表达一种常见形式的 癫痫意味着我们现在可以用这个基因位点作为探针， 表达可能受同一基因影响的其他癫痫 基因座 这意味着我们现在有了一种分类广义 基于病因而非特异性临床症状的癫痫。 此外，鉴定出与异常脑电图有关的基因意味着， 一旦知道了基因产物，大脑工作的基本方面 可以进行调查。

Juvenile myoclonic epilepsy (JME) or the syndrome of Janz, is a clinically well-defined benign form of epilepsy that starts in adolescence. It is characterized by small myoclonic jerks, clonic-tonic-clonic-seizures, and a characteristic EEG feature -4-6 Hz multispike-wave complexes (4-6 Hz mS&W). JME occurs more frequently in the relatives of JME patients than in the general population, as do other forms of epilepsy. In addition, the 4-6 Hz mS&W and other EEG abnormalities occur in family members without epilepsy. JME is a common form of epilepsy, thought to represent about 100% of all epilepsies. We recently reported the finding of strong evidence for linkage of JME traits seen in relatives to the HLA and BF loci on chromosome 6. The lod score is over 3.0 no matter what mode of inheritance is assumed when we classify the abnormal EEGs seen in unaffected family members as "affected". The lod score also remains over 3.0 no matter how family members with non-JME epilepsy are classified. Under the most conservative classification (non-JME epilepsy considered "unaffected") the lod score is over 4.0 under recessive inheritance. A preliminary segregation analysis showed a two locus model for JME could be rejected. The current study is designed to confirm and further investigate the genetics of both JME and the relationship of JME to other generalized epilepsy. JME probands will be identified in clinics in the New York area. We will investigate the inheritance of JME and the EEG traits by analysis of the linkage marker data as well as by segregation analysis. We will gather data from 125 JME families over five years. In addition to the JmE families, we will collect data on 30 families identified through a patient with juvenile absence and 30 through a patient with tonic-clonic seizures. These data will allow us to test for heterogeneity between JME and other forms of epilepsy and to test whether a subgroup of those non- JME families map to chromosome 6. We will use HLA typing and restriction fragment length polymorphisms (RFLP) for mapping, with RFLP probes derived initially from the around the HLA region. We will look for genetic linkage markers closer to the locus for JME and the EEG traits. The identification of a genetic marker for JME has given a new focus to basic studies on the classification and mechanisms of the epilepsies. The identification of a gene involved in the expression of a common form of epilepsy means that we can now use that gene locus as a probe to identify other epilepsies whose expression may be influenced by the same gene locus. This means that we now have a way of classifying the generalized epilepsies based on etiology rather than non-specific clinical symptoms. Also, the identification of a gene involved in abnormal EEGs means that, once the gene product is known, a basic aspect of the working of the brain can be investigated.