Families At Risk: Long-term Impact of Huntington's Presymptomatic Genetic Testi

描述(申请人提供)：亨廷顿病(HD)几十年来一直是我们如何思考基因测试及其对被测试个人及其家人的好处和风险的典范。1983年，HD的基因被定位在4号染色体上，从而开发了用于HD症状前基因测试的连锁测试。1986年，约翰斯·霍普金斯大学在美国启动了两个此类测试项目之一。这项工作影响了提供HD基因测试结果的指南，随后也影响了其他成人起病的神经退行性疾病的当代指南。可以说，这一早期经验也影响了我们对与基因检测和提供基因检测结果有关的许多问题的集体思考。近30年后，我们仍然与这一早期群体中的许多成员保持联系。随着越来越多的基因测试被用于预测成人起病的神经退行性疾病，随着大规模基因测试越来越多地被整合到临床护理中，我们不仅要了解症状前测试对高危个人几年的影响，而且要了解高危个人及其家人在其一生中的含义。在这里，我们有一个独特的机会 回顾几十年来，高危个体及其家人是如何沟通和处理测试结果的，不是在测试后的几个月或几年，而是测试后的几十年。我们将通过对一部分高危个人进行深入采访来实现这一点 在1986年至1996年期间进行了测试，以受试者家庭成员的子集为对象的焦点小组，以及向1986年至1996年期间接受测试的所有高危个人及其家庭成员发送的调查。这项研究的结果将提高我们对严重的、目前无法治愈的疾病的基因检测结果如何在家庭内和通过家庭传达的理解，这些信息如何影响选择(例如，职业、参与研究、 这将有助于了解高危个人及其家庭几十年来的发展轨迹，并将有助于为宣传这些成果的政策和程序提供信息。在具体目标1下，我们将探讨亨廷顿病(HD)症状前基因检测在检测18-28年后对高危个体的生活和选择的影响。在具体目标2下，我们将建立在与该队列的先前工作的基础上，以确定个体在经历生命阶段的过程中对其测试经验的感觉和理解的纵向变化。在具体目标3下，我们将探讨HD症状前基因检测在检测18-28年后对受试者的家庭成员(配偶、伴侣、子女)的影响。在具体目标4下，我们将以目标1-3的结果为基础，探讨个人及其家庭的意见如何与目前进行临床遗传和基因组检测的范例和政策相一致。

DESCRIPTION (provided by applicant): Huntington's disease (HD) has for decades served as a model for how we think about genetic testing, and its benefits and risks for tested individuals and their families. In 1983, the gene for HD was mapped to chromosome 4, allowing linkage tests to be developed for use in presymptomatic genetic testing for HD. In 1986, Johns Hopkins launched one of the first two such testing programs in the United States. This work influenced guidelines for the provision of HD genetic test results, which have subsequently influenced contemporary guidance for other adult-onset neurodegenerative diseases. This early experience also arguably influenced our collective thinking about many issues related to genetic testing and the provision of genetic test results. Almost 30 years later, we are still in contact wth many members of this early cohort. As increasing numbers of genetic tests are being used to predict adult-onset neurodegenerative disease, and as large-scale genetic testing is increasingly integrated into clinical care, it is critical that we understand not only the implicatons of presymptomatic testing for the at-risk individual over several years, but also for the at-risk individual and her/his family over the course of their lives. Here, we have a unique opportunity to take a retrospective look over decades at how at-risk individuals and their families communicate about and cope with test results not months or years following testing, but decades following testing. We will do this through in-depth interviews with a subset of those at-risk individuals who were tested between 1986 and 1996, focus groups with a subset of family members of tested individuals, and a survey sent to all at-risk individuals who were tested from 1986 to 1996 and their family members. The outcomes of this research will improve our understanding of how the results of genetic testing for serious, currently incurable disease are communicated in and through families, how this information influences choices (e.g., career, participation in research, having children) and trajectories of at-risk individuals and their families over decades, and will help inform policies and procedures for communicating such results. Under Specific Aim 1, we will explore the impact of presymptomatic genetic testing for Huntington's disease (HD) on the lives and choices of at-risk individuals, 18-28 years after testing. Under Specific Aim 2, we will build on prior work with this cohort to determine longitudinal changes in individuals' feelings about and understanding of their testing experience as they have progressed through life's stages. Under Specific Aim 3, we will explore the impact of presymptomatic genetic testing for HD on family members (spouses, partners, children) of tested individuals, 18-28 years after testing. Under Specific Aim 4, we will build on the results of Aims 1-3 to explore how the views of individuals and their families comport with the current paradigms and policy for the conduct of clinical genetic and genomic testing.