PRESYMPTOMATIC DNA TESTING FOR HUNTINGTON'S DISEASE

已经发现了一些神经精神疾病的遗传联系 紊乱在许多情况下，这些发现将允许开发 症状前诊断测试这样的测试将使研究人员 来研究那些被确定为处于高水平的人的疾病演变， 遗传风险更重要的是，症状前的疾病检测将 指导治疗、早期干预和预防工作。一直 然而，人们非常担心， 揭示了高遗传风险，特别是对于目前无法治愈的 疾病。 一项关于使用关联的基因检测亨廷顿病（HD）的研究计划 4号染色体标记始于1986年。本研究的目的 已经确定：1）是否有和没有连接的DNA 他们的基线神经心理学和精神病学标记不同 特征，2）心理和社会后果 症状前诊断，3）基线特征是否可以 预测这些后果在个别情况下，和4）是否预先 测试教育和咨询以及测试后的临床随访可以 预防或减轻病态反应。到目前为止，74名健康人处于危险之中， 已经进行了信息性测试，另外42名希望遗传 测试在协议中。 在该计划的拟议五年延续期内， 受试者将进入测试方案。所有受试者将 继续接受神经学、精神病学的评估， 在DNA测试披露后定期进行神经心理学检查 结果该应用程序还包含两个新举措。一是 将使用（15）O标记水检查局部脑血流 当HD标志物检测呈阳性时， 他们开始在神经、情感或 认知状态这将使我们能够确定哪些小症状 在测试后预示着疾病的发作，并将使我们能够测试假设 关于局部脑血流改变 临床综合症的特殊方面。第二个新 该倡议包括关于风险计算的数据分析研究， 基于链接结果的HD。使用测试的真实的数据 家系和模拟数据，对风险估计的影响， 这些因素如所用标记的数量，假定的等位基因频率， 亲子鉴定的错误，以及亲属对HD的误诊， 被评价。

Genetic linkages have been found to a number of neuropsychiatric disorders. In many cases, these discoveries will allow the development of presymptomatic diagnostic tests. Such testing will enable researchers to study the evolution of disease in those determined to be at high genetic risk. More importantly, presymptomatic detection of disease will guide treatment, early intervention, and prevention efforts. There has been great concern, however, about potential harmful effects of disclosing high genetic risk, especially for currently-incurable illnesses. A research program on testing for Huntington's disease (HD) using linked chromosome-4 markers was initiated in 1986. The purpose of this research has been to determine: 1) whether those with and without the linked DNA marker differ in their baseline neuropsychological and psychiatric characteristics, 2) the psychological and social consequences of presymptomatic diagnosis, 3) whether baseline characteristics can predict those consequences in individual cases, and 4) whether pre- testing education and counseling and post-test clinical follow-up can prevent or palliate morbid responses. To date, 74 healthy people at risk for HD have had informative tests, and another 42 who want genetic testing are in the protocol. In the proposed five-year continuation of this program, 90 new at-risk subjects will be entered into the testing protocol. All subjects will continue to be evaluated neurologically, psychiatrically, and neuropsychologically at regular intervals after disclosure of DNA test results. This application also contains two new initiatives. First, we will examine regional cerebral blood flow using the (15)O-labeled water PET technique in those subjects who test positive for the HD marker when they begin to display subtle changes in neurologic, affective, or cognitive status. This will enable us to determine which minor symptoms after testing herald disease onset, and will allow us to test hypotheses concerning the association of regional cerebral blood flow alterations with particular aspects of the clinical syndrome. The second new initiative consists of data analytic studies on the calculation of risk for HD based on linkage results. Using both real data from tested pedigrees and simulated data, the influence on estimation of risk of such factors as number of markers used, assumed allele frequencies, errors in ascribing paternity, and misdiagnosis of HD in relatives will be evaluated.