PRESYMPTOMATIC DNA TESTING FOR HUNTINGTON'S DISEASE

分子遗传学的进展将很快使症状前诊断成为可能 (或确定)大量的遗传风险增加 神经精神障碍。这样的测试将使研究人员能够研究 那些被确定为高遗传风险的人的疾病演变。 更重要的是，对疾病的症状前检测将指导治疗， 早期干预和预防努力。 A-使用LINK测试亨廷顿病(HD)的研究计划 1986年9月，约翰霍普金斯大学建立了DNA标记。 本研究的目的是确定：1)心理健康状况 和症状前诊断的社会后果，2)是否预先测试 特征可以在个别情况下预测这些后果，以及3) 无论是检测前的教育和咨询，还是检测后的临床随访- UP可以防止或缓解病态反应。到目前为止，38名健康人在 Risk for HD已经进行了信息丰富的预测测试，另有41人希望 基因检测也在协议中。 在这一计划的拟议延续中，我们将大幅增加 受试样本。我们将招收150名新的高危对象，并继续 评估所有测试对象(以及那些没有提供信息的测试和 那些未测试的控制组)在测试后定期进行 发现一个人对自己遗传状态的了解所产生的心理反应。 我们预测：1)那些标志物检测呈阳性的人，作为一名 测试后，比那些测试的人稍微更痛苦 阴性，但将保持在心理测试和正常范围内 精神病学访谈，以及2)社会变量、个性 基因检测前的心理困扰会 预测心理和社会结果。大多数测试的人 遗传标记呈阳性，以及单独匹配的样本 那些检测呈阴性的人，将每半年进行一次神经学，精神病学， 和神经心理评估，以及每年的核磁共振扫描 定量脑体积研究和18F-2-脱氧葡萄糖PET扫描 评估局部脑代谢的变化。使用这些 技术，我们希望能够记录最早的表现形式 疾病发作的可能性。需要检验的假设是，那些测试的人 标记物阳性将显示尾状核的形态变化 PET出现前的MRI和纹状体糖代谢降低 HD在确定症状前需求的大小方面存在风险 测试和决定人们是否存在其他风险的变量 神经精神障碍将寻求预测性DNA测试。

Advances in molecular genetics will soon allow presymptomatic diagnosis of (or determination of increased genetic risk for) a large number of neuropsychiatric disorders. 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. A-research program on testing for Huntington's disease (HD) using linked DNA markers was established at Johns Hopkins University in September 1986. The purpose of this research has been to determine: 1) the psychological and social consequences of presymptomatic diagnosis, 2) whether pre-testing characteristics can predict those consequences in individual cases, and 3) whether pre-testing education and counseling and post-test clinical follow- up can prevent or palliate morbid responses. To date, 38 healthy people at risk for HD have had informative predictive tests, and another 41 who want genetic testing are in the protocol. In the proposed continuation of this program, we will greatly increase the subject sample. We will enroll 150 new at-risk subjects and continue to evaluate all subjects tested (as well as those with uninformative tests and those who are non-tested controls) at regular intervals after testing to discover the psychological responses to knowledge of one's genetic status. We predict that: 1) those who test positive for the marker will, as a group, be slightly more distressed after testing than those who test negative, but will remain within normal limits on psychological tests and psychiatric interviews, and 2) social variables, personality characteristics, and psychological distress prior to genetic testing will be predictive of psychological and social outcome. Most of those who test positive for the genetic marker, and an individually-matched sample of those who test negative, will have semi-annual neurological, psychiatric, and neuropsychological evaluations, as well as annual MRI scans for quantitative brain volumetric studies and 18F-2-deoxyglucose PET scans for assessment of changes in regional brain metabolism. Using these techniques, we hope to be able to document the very earliest manifestations of disease onset. The hypothesis to be tested is that those who test positive for the marker will display morphologic changes in the caudate on MRI and reduced striatal glucose metabolism on PET prior to the emergence at risk for HD to determine the magnitude of the demand for presymptomatic testing and the variables that determine whether people risk for other neuropsychiatric disorders will seek predictive DNA testing.