Age-based genomic screening in newborns, infants, and children: a novel paradigm in public health genomics

项目总结/摘要 基因组测序为识别临床相关的遗传变异提供了前所未有的机会， 在这项技术能够常规地应用于健康领域之前， 人口，以确定个人与可采取行动的障碍，及时预防或改善症状。这 该项目探索了一种创新的基于年龄的基因组筛选（ABGS）模式，旨在提供有针对性的 和高度可操作的遗传信息的父母通过他们的孩子的例行健康访问，从而避免 基因组规模测序的一些更困难的方面，同时保留大部分的好处。我们将 利用已建立的指标，评估与“临床可行性”相关的参数，并定义年龄 发病和/或干预年龄，以确定适用于筛查的条件。在 与一个多元化的专家审议小组合作，我们将确定一个共识框架， 在婴儿期和儿童期的特定时间点使用靶向测序板的ABGS程序。 我们将与社区利益相关者合作，提高对ABGS计划的认识，并获得关键反馈 为编写无障碍学习材料提供信息。我们将应用遗传医学实施 研究框架并利用严格的方法和措施来识别潜在的障碍和促进因素 并制定解决这些问题的战略。最后，我们将在少数小学进行试点项目， 评估初步结果的护理儿科诊所，包括父母和提供者的观点，以及 ABGS的可行性、可接受性和实用性。这一建议的预期结果是一个经过验证的， 知识产权人知情的，实用的ABGS计划，包括数百种可操作的条件 在整个生命周期中，为未来在更多实践中进行纵向研究奠定了基础， 评估临床和卫生经济结果。在这项工作中，我们将雇用一个以社区为基础的 参与式研究方法，寻求不同利益攸关方的观点，并强调 在广泛的环境中研究ABGS的重要性。这项研究计划的长期目标是 创建一个广泛适用的基因组筛查计划，该计划远远超出了新生儿筛查， 将其纳入常规的良好儿童护理中。我们设想，这个计划也将准备个人， 最终就成人发病筛查的潜在益处和风险做出明智的决定 研究人员还发现，在成年期的条件下，从而在所有年龄组的基因组筛查工作之间建立联系。

Project Summary/Abstract Genomic sequencing offers an unprecedented opportunity to identify clinically relevant genetic variants, yet there are many challenges to overcome before this technology can be applied routinely in the healthy population to identify individuals with actionable disorders in time to prevent or ameliorate symptoms. This project explores an innovative age-based genomic screening (ABGS) paradigm that aims to provide targeted and highly actionable genetic information to parents via their child’s routine wellness visits, thereby avoiding some of the more difficult aspects of genome-scale sequencing while retaining most of the benefits. We will utilize an established metric that evaluates parameters relevant to “clinical actionability” and defines the age of onset and/or the age of intervention, to identify conditions that would be applicable for screening. In collaboration with a diverse Expert Deliberative Group, we will define a consensus framework for carrying out the ABGS program using targeted sequencing panels at specified time-points during infancy and childhood. We will engage community stakeholders to raise awareness of the ABGS program and obtain critical feedback to inform the development of accessible study materials. We will apply the Genetic Medicine Implementation Research framework and utilize rigorous methods and measures to identify potential barriers and facilitators and develop strategies to address them. Finally, we will conduct a pilot project in a small number of primary care pediatrics clinics assessing preliminary outcomes, including perspectives of parents and providers, and the feasibility, acceptability, and utility of ABGS. The expected result of this proposal is a validated, stakeholder-informed, and practical ABGS program that includes hundreds of conditions that are actionable throughout the lifespan, setting the stage for a future longitudinal study in a larger number of practices that can assess clinical and health economic outcomes. Throughout this work, we will employ a community-based participatory research approach to seek out perspectives from diverse stakeholders and emphasize the importance of studying ABGS in a wide range of settings. The long-term goal of this research program is to create a broadly applicable genomic screening program that extends well beyond newborn screening and can be incorporated into routine well child care. We envision that this program will also prepare individuals to eventually make informed decisions about the potential benefits and risks of screening for adult-onset conditions during adulthood, thus creating a connection between genomic screening efforts in all age groups.