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

面临风险的家庭：亨廷顿舞蹈症症状前基因测试的长期影响

• 批准号: 9458364
• 负责人: DEBRA JH MATHEWS
• 金额: $ 10.5万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9458364
• 关键词: Adult; Benefits and Risks; Child; Chromosomes; Chromosomes, Human, Pair 4; DNA; Disease; Family; Family member; Feeling; Focus Groups; Genetic; Genetic Polymorphism; Genetic screening method; Genomics; Guidelines; Hereditary Disease; Huntington Disease; Huntington gene; Individual; Interview; Learning; Life; Maps; Medical Genetics; Modeling; Neurodegenerative Disorders; Outcomes Research; Policies; Procedures; Research; Risk; Spouses; Surveys; Test Result; Testing; Thinking; Time; United States; Work; career; clinical care; cohort; design; early experience; exome sequencing; experience; genome sequencing; improved; member; presymptomatic testing; programs; public health relevance

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.

描述（由申请人提供）：几十年来，亨廷顿氏舞蹈病 (HD) 一直是我们如何看待基因检测及其对受检个人及其家庭的益处和风险的模型。 1983 年，HD 基因被定位到 4 号染色体，从而可以开发用于 HD 症状前基因检测的连锁测试。 1986 年，约翰·霍普金斯大学在美国启动了首批两个此类测试项目之一。这项工作影响了 HD 基因检测结果的提供指南，随后又影响了当代其他成人发病的神经退行性疾病的指南。这种早期的经历也可以说影响了我们对与基因检测和提供基因检测结果相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的许多成员保持联系。 随着越来越多的基因检测被用来预测成人发病的神经退行性疾病，并且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数年的影响，而且还要了解高危个体及其家人一生的影响，这一点至关重要。在这里，我们有一个独特的机会 回顾几十年来，高危个人及其家人如何沟通和应对测试结果，而不是测试后数月或数年，而是测试后数十年。我们将通过对一部分高危人群进行深入访谈来做到这一点 1986 年至 1996 年期间进行了测试，焦点小组由测试者的一部分家庭成员组成，并向 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了一份调查。这项研究的结果将提高我们对目前无法治愈的严重疾病的基因检测结果如何在家庭中和通过家庭进行交流的理解，以及这些信息如何影响选择（例如职业、参与研究、 生育孩子）以及高危个人及其家庭几十年来的轨迹，并将有助于为传达此类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 年后高危人群的生活和选择的影响。在具体目标 2 下，我们将在之前与该群体合作的基础上，确定个人在经历人生阶段时对其测试经历的感受和理解的纵向变化。在具体目标 3 下，我们将探讨 HD 症状前基因检测对检测后 18-28 岁的受检测者家庭成员（配偶、伴侣、子女）的影响。在具体目标 4 下，我们将在目标 1-3 的结果的基础上探讨个人及其家人的观点如何与当前进行临床遗传和基因组测试的范式和政策相一致。