PRESYMPTOMATIC DNA TESTING FOR HUNTINGTON'S DISEASE

已发现基因与许多神经精神疾病有关 精神错乱。在许多情况下，这些发现将使 症状前诊断测试。这样的测试将使研究人员能够 研究被确定为高血压者的疾病演变 遗传风险。更重要的是，症状前疾病的检测将 指导治疗、早期干预、预防工作。那里有 然而，我一直非常担心， 暴露出高遗传风险，特别是对目前无法治愈的 疾病。 使用LINK进行亨廷顿病(HD)检测的研究计划 4号染色体标记诞生于1986年。这项研究的目的是 已经确定：1)那些有和没有连接的DNA的人 标记物在基线、神经心理学和精神病学方面不同 特征，2)心理和社会后果 症状前诊断，3)基线特征是否可以 在个别情况下预测这些后果，以及4)是否预先 检测教育和咨询以及检测后的临床随访可以 防止或减轻病态反应。到目前为止，74名健康的人处于危险之中 对于HD已经进行了信息丰富的测试，另有42人想要基因 测试是在协议中规定的。 在这一计划的拟议五年延续中，90个新的风险 受试者将被录入测试方案。所有受试者都将 继续接受神经学、精神病学和 DNA检测结果公布后定期进行神经心理检查 结果。该应用程序还包含两个新计划。首先，我们 将使用(15)O标记的水检查局部脑血流 PET技术在HD标志物检测阳性的受试者中的应用 他们开始表现出神经、情感或 认知状态。这将使我们能够确定哪些轻微症状 在测试先兆疾病发作之后，并将允许我们测试假设 关于局部脑血流改变的关联性 与临床综合征的特定方面有关。第二条新消息 倡议由关于风险计算的数据分析研究组成 基于链接结果的HD。使用来自测试的两个真实数据 家系和模拟数据对风险估计的影响 这些因素包括使用的标记数量、假设的等位基因频率、 亲人遗嘱中对亲子关系的错误和HD的误诊 被评估。

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.