GENETICS OF AD PARTIAL EPILEPSY WITH AUDITORY FEATURES

描述：应用程序建议继续进行调查 新发现的常染色体显性遗传性(AD)癫痫综合征 听觉功能(ADPEAF)。这种综合征的易感基因是 最近被定位在染色体10q的一个10厘米的区域。这个 目前的计划是确定并临床表现出5-10个额外的 ADPEAF的扩展家系，包括大约100名在世受试者 (35个受影响)，并确认和完善 对这些家系的易感基因进行连锁分析。 将通过四种方法确定家庭：1)筛查 申请机构的癫痫患者计算机数据库；2) 每年寄给美国癫痫学会会员的邮件；3) 在《癫痫美国报》上发表文章 美国基金会；以及4)提交演示文稿请求 由申请人提交。 只有包含3个或更多的族时，才会将其包括在分析中 具有听觉特征的部分性癫痫患者，类似于 在这项研究的原始谱系中。申请者将测试每个人 与染色体10q上相同标记和相同标记连锁的家族 遗传模型与前面的分析相同。如果存在关联的证据是 发现，他们将搜索重组事件，进一步缩小 包含轨迹的区域。将通过以下方式评估局部异质性 确定有证据表明与癌症有关的家庭比例 染色体10q与ADPEAF易感基因的定位 没有显示出连锁证据的家庭中的地区。在家庭中，有 与染色体10q连锁的证据，申请者将测试 易感基因增加其他癫痫风险的假说 除ADPEAF外的其他疾病(例如，全身性癫痫、孤立性癫痫 无端癫痫、发热性惊厥和/或与酒精有关的癫痫)， 通过比较个体中受这些疾病影响的比例 很可能，也不太可能是基因携带者。

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.