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

描述（由申请人提供）：几十年来，亨廷顿舞蹈病（HD）一直是我们如何看待基因检测的模式，以及它对被检测个体及其家庭的益处和风险。1983年，HD基因被定位到4号染色体上，使得连锁检测得以发展，用于HD症状前基因检测。1986年，约翰霍普金斯大学启动了美国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。这种早期的经历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年过去了，我们仍然与这一早期群体的许多成员保持着联系。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，随着大规模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，而且要了解高危个体及其家庭在其一生中的影响。在这里，我们有一个独特的机会

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.