GENETICS OF AD PARTIAL EPILEPSY WITH AUDITORY FEATURES

描述：申请建议继续进行调查 新发现的常染色体显性（AD）癫痫综合征， 听觉特征（ADPEAF）。 这种综合征的易感基因是 最近定位于染色体10号的10厘摩区域。 的 目前的计划是确定和临床表征5-10个额外的 ADPEAF扩展家系，包括约100例存活受试者 (35受影响的），并确认和完善本地化的 易感基因进行连锁分析。 将通过四种方法确定家庭：1）筛选 申请机构的癫痫患者计算机化数据库; 2） 每年向美国癫痫协会会员发送邮件; 3） 发表一篇文章在美国癫痫，报纸的癫痫 美国基金会;以及4）在介绍中要求转介 由申请人。 只有当家族包含3个或更多时，才将其纳入分析 具有听觉特征的部分癫痫患者，类似于 在这项研究的原始谱系中。 申请人将测试每个 与染色体10 q上的相同标记连锁的家族， 遗传模型与前面的分析一样。 如果有证据表明 发现，他们将寻找重组事件，进一步缩小 包含轨迹的区域。 局部异质性将通过以下方式进行评估： 确定有证据表明与家庭暴力有关的家庭比例， 染色体10 q和定位ADPEAF的易感基因到其他 家庭中没有显示出联系证据的区域。 家庭的 与染色体10 q连锁的证据，申请人将测试 易感基因增加其他癫痫发作风险的假说 除了ADPEAF之外的疾病（例如，全身性癫痫，孤立性 无端惊厥、热性惊厥和/或酒精相关惊厥）， 通过比较个体之间受这些疾病影响的比例， 可能是基因携带者，也可能不是。

DESCRIPTION: The application proposes to continue an ongoing investigation of a newly identified autosomal dominant (AD) epilepsy syndrome with auditory features (ADPEAF). A susceptibility gene for this syndrome was recently localized to a 10 centimorgan region of chromosome 10q. The current plan is to ascertain and clinically characterize 5-10 additional extended pedigrees with ADPEAF, comprising approximately 100 living subjects (35 affected), and to confirm and refine the localization of the susceptibility gene by performing linkage analysis in these families. Families will be ascertained through four methods: 1) screening of the computerized database of epilepsy patients at the applicant institution; 2) yearly mailings to the membership of the American Epilepsy Society; 3) publication of an article in Epilepsy USA, the newspaper of the Epilepsy Foundation of America; and 4) requests for referrals in presentations given by the applicant. Families will be included in the analysis only if they contain 3 or more individuals with partial epilepsy with auditory features, similar to those in the original pedigree of this study. The applicants will test each family for linkage with the same markers on chromosome 10q and the same genetic model as in the previous analysis. If evidence for linkage is found, they will search for recombination events that further narrow the region containing the locus. Local heterogeneity will be assessed by determining the proportion of families with evidence for linkage to chromosome 10q and localizing susceptibility genes for ADPEAF to other regions in families that do not show evidence for linkage. In families with evidence for linkage to chromosome 10q, the applicants will test the hypothesis that the susceptibility gene raises risk for other seizure disorders in addition to ADPEAF (e.g., generalized epilepsies, isolated unprovoked seizures, febrile convulsions, and/or alcohol-related seizures), by comparing the proportion affected with these disorders among individuals likely, and not likely, to be gene carriers.