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

描述（由申请人提供）：几十年来，亨廷顿病（HD）一直是我们如何看待基因检测及其对受试个体及其家庭的益处和风险的模型。1983年，HD的基因被定位在4号染色体上，使得连锁测试能够被开发用于HD的症状前基因测试。1986年，约翰霍普金斯大学在美国启动了最早的两个此类测试项目之一。这项工作影响了提供HD基因检测结果的指南，随后影响了其他成人发病神经退行性疾病的当代指南。这种早期的经验也可以说影响了我们对许多与基因检测和提供基因检测结果有关的问题的集体思考。近30年后，我们仍然与这个早期群体的许多成员保持联系。 随着越来越多的基因检测被用于预测成人发病的神经退行性疾病，以及大规模的基因检测越来越多地融入临床护理，我们不仅要了解症状前检测对高危个体的影响，而且还要了解高危个体及其家人在其一生中的影响。在这里，我们有一个独特的机会， 回顾几十年来，高危人群及其家人如何沟通和应对检测结果，而不是检测后的几个月或几年，而是检测后的几十年。我们将通过深入采访一部分高危人群来做到这一点， 在1986年至1996年之间进行了测试，焦点小组与测试个人的家庭成员的子集，并向1986年至1996年进行测试的所有高危个人及其家庭成员发送了一份调查。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是如何在家庭中和通过家庭传播的，这些信息如何影响选择的理解（例如，职业生涯，参与研究， 该研究将有助于为宣传这些结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）症状前基因检测对检测后18 - 28年高危人群生活和选择的影响。根据具体目标2，我们将建立在以前的工作与这个队列，以确定纵向变化的个人的感觉和理解他们的测试经验，因为他们已经通过生活的各个阶段的进展。在具体目标3下，我们将探讨HD症状前基因检测对检测后18 - 28年受检者家庭成员（配偶、伴侣、子女）的影响。在具体目标4下，我们将在目标1 - 3的结果基础上，探索个人及其家庭的观点如何符合当前进行临床遗传和基因组检测的范式和政策。

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.