NC NEXUS, North Carolina Newborn Exome Sequencing for Universal Screening

NC NEXUS，北卡罗来纳州新生儿外显子组测序，用于通用筛查

• 批准号: 8915731
• 负责人: JONATHAN S BERG
• 金额: $ 115.94万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-05 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8915731
• 关键词: Address; Child; Child health care; Childhood; Clinical; Decision Making; Development; Diagnostic; Disease; Ethics; Evidence Based Medicine; Family; Future; Genome; Genomics; Incidental Findings; Individual; Infant; Laboratories; Medicine; Neonatal Screening; Newborn Infant; North Carolina; Patients; Population; Prevention; Public Health; Rights; Sensitivity and Specificity; Technology; Testing; Variant; Vulnerable Populations; accurate diagnosis; base; clinical application; cohort; deep sequencing; ethical legal social implication; exome sequencing; genome sequencing; genome-wide; improved; insight; interdisciplinary approach; interest; meetings; named group; new technology; novel; screening; tool

DESCRIPTION (provided by applicant): Since newborn screening (NBS) began in the 1960's, technological advances have resulted in its use in an increasing number of disorders. Recent developments in whole genome sequencing and its simpler corollary, whole exome sequencing (WES), now afford the opportunity to comprehensively define the variation within an individual's genome in a rapid and affordable manner. Many challenges arise with the clinical application of genome-scale sequencing and in deriving practical benefit to infants and children. Its utility in NBS has yet to be demonstrated and its application in the pediatric population requires special examination, not only for potential clinical benefits, but also for the unique ethical challenges it presents. In this proposal, we outline a highly interdisciplinary approach to identifying, confronting and overcoming the major challenges that must be met in order to implement deep sequencing technology to enhance current newborn screening in a diverse pediatric population. Overarching Aim 1 will evaluate the utility of WES as a diagnostic tool to extend the utility of current NBS. Using diverse cohorts of infants and young children with known conditions identified through NBS, we will examine the sensitivity and specificity of WES. We will also utilize WES in cohorts of children with known conditions not currently screened for as potential candidates for NBS in the future. Overarching Aim 2 will develop and assess a framework for analyzing WES in a clinically oriented framework based on principles of ethics and evidence-based medicine. We will develop strategies to guide clinicians, clinical laboratories and patients/families in their decisions regarding the inevitable incidental findings that will be detected in ways that respect the child and protect his/her future autonomy, while also respecting parental interests and rights. Overarching Aim 3 will explore ethical, legal and social issues (ELSl) involved in informed decision-making and develop best practices regarding return of results after testing. We will develop novel decision support tools and evaluate their usefulness in parental decision making, and examine the burdens placed on clinicians as this new technology is deployed in the vulnerable and special population that are newborns and their families.

描述（由申请人提供）：自 20 世纪 60 年代开始新生儿筛查 (NBS) 以来，技术进步导致其在越来越多的疾病中得到应用。全基因组测序及其更简单的推论、全外显子组测序 (WES) 的最新发展，现在提供了以快速且经济实惠的方式全面定义个体基因组内变异的机会。基因组规模测序的临床应用以及为婴儿和儿童带来实际益处时出现了许多挑战。它在 NBS 中的效用尚未得到证实，其在儿科人群中的应用需要特殊检查，不仅是为了潜在的临床益处，而且是为了它带来的独特的伦理挑战。在本提案中，我们概述了一种高度跨学科的方法 识别、面对和克服必须应对的主要挑战，以实施深度测序技术，以加强当前不同儿科人群的新生儿筛查。总体目标 1 将评估 WES 作为诊断工具的效用，以扩展当前 NBS 的效用。我们将使用通过 NBS 确定的患有已知病症的不同婴儿和幼儿群体来检查 WES 的敏感性和特异性。我们还将在目前尚未筛选为 NBS 未来潜在候选者的已知病症儿童队列中使用 WES。总体目标 2 将开发和评估一个框架，用于在基于伦理和循证医学原则的临床导向框架中分析 WES。我们将制定策略，指导临床医生、临床实验室和患者/家属就不可避免的偶然发现做出决定，这些偶然发现将以尊重儿童和保护他/她未来自主权的方式进行发现，同时也尊重父母的利益和权利。总体目标 3 将探讨知情决策中涉及的道德、法律和社会问题 (ELSl)，并制定有关测试后返回结果的最佳实践。我们将开发新颖的决策支持工具，并评估其在父母决策中的有用性，并检查当这项新技术部署在新生儿及其家人等弱势和特殊人群中时给临床医生带来的负担。