RESOLVING HETEROGENEITY IN EPILEPSY WITH GENETIC MARKERS

青少年肌阵挛癫痫(JME)或Janz综合征，是一种临床表现 定义明确的良性癫痫，始于青春期。它是 以小的肌阵挛、阵挛-强直-阵挛发作为特征，以及 脑电特征--4-6赫兹多棘波复合波(4-6赫兹 MS&W)。JME患者亲属中发生JME的频率高于 在普通人群中，其他形式的癫痫也是如此。此外, 4-6 Hzms&W和其他脑电异常发生在家族成员中 没有癫痫。JME是癫痫的一种常见形式，被认为代表 大约100%的癫痫患者。 我们最近报告了JME连锁的强有力证据的发现 6号染色体上与人类白细胞抗原和BF基因座相关的性状 无论我们假设什么继承模式，得分都在3.0以上 将未受影响的家庭成员出现的异常脑电分类为 “受影响”。Lod得分也保持在3.0以上，无论怎样的家庭 对非JME癫痫患者进行分类。在最保守的 分类(非JME癫痫被认为是“未受影响的”)LOD评分为 隐性遗传超过4.0。关于偏析的初步分析 表明JME的双轨迹模型是可以拒绝的。 目前的研究旨在证实和进一步调查 JME的遗传学及其与其他广义遗传病的关系 癫痫。JME先证者将在纽约的诊所被确认 区域。我们将通过以下方法研究JME和EEG特征的遗传 对连锁标记数据的分析以及分离分析。 我们将在五年内收集125个JME家庭的数据。除了……之外 JME家庭，我们将收集通过 青少年缺席患者30例，强直阵挛患者30例 癫痫发作。这些数据将使我们能够测试JME之间的异构性 和其他形式的癫痫，并测试这些非癫痫患者的一个子组是否 JME家系定位于6号染色体。我们将使用人类白细胞抗原分型和限制性内切酶 用于作图的片段长度多态(RFLP)，以及衍生的RFLP探针 最初来自于人类白细胞抗原区域周围。我们将寻找基因 连锁标记更接近于JME和EEG性状的基因座。 JME遗传标记的发现为JME的研究提供了新的焦点 癫痫分类及发病机制的基础研究。这个 一个涉及一种常见形式的表达的基因的鉴定 癫痫意味着我们现在可以使用这个基因位点作为探针来识别 表达可能受同一基因影响的其他癫痫 轨迹。这意味着我们现在有了一种将泛化的 癫痫基于病因而不是非特定的临床症状。 此外，识别与异常脑电有关的基因意味着， 一旦知道了基因产物，大脑工作的一个基本方面 可以被调查。

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.