Regional Cystic fibrosis DNA Mutation Analysis

描述（由申请人提供）：本项目的目标是通过建立一个区域性囊性纤维化（CF）检测实验室，提高纽约中大西洋遗传和新生儿筛查服务联盟（NYMAC）第2区域内囊性纤维化（CF）筛查的效率。囊性纤维化是2006年美国医学遗传学学会（ACMG）报告中列出的29种核心疾病之一，新生儿筛查，走向统一的筛查小组和系统。2006; 8（5）增刊：S12-S252.] CF突变测试已被推荐并在美国约一半的州实施。尚未实施CF突变检测的州，许多是强制性的两个样本州，可能无法这样做，因为最近经济环境的低迷阻止了其新生儿筛查（NBS）系统的进一步增强。通过在该地区提供免费的CF-DNA突变检测，我们将能够确认初级IRT检测并减少假阳性结果。阳性预测值将得到改善，该地区对汗液测试的需求将最小化。为了实现这一目标，将选择一个供应商，该供应商拥有现成的产品，这些产品具有广泛的突变，涵盖美国东北部常见的种族群体，有限的前端支出，以及适合目前NBS工作量的处理。已经询问了一些州，NYMAC地区的四个州有可能从这些服务中受益：特拉华州、马里兰州、新泽西和弗吉尼亚州。其中三个州使用IRT/IRT算法进行CF测试，一个州仅对F508进行IRT，然后进行CF-DNA测试。特拉华州公共卫生实验室（DPHL）将进行方法验证，聘请合同分子生物学家，提供实验室空间，制定时间轴，获得并安装必要的设备，确保培训，并制定使该项目成功所需的工作流程和报告系统。与此同时，该项目还将探讨在纽约海事中心区域集中进行这一测试的有效性。 公共卫生相关性：该项目致力于“健康人民2010”的孕产妇、婴儿和儿童健康优先领域，以减少胎儿和婴儿死亡，并通过扩大囊性纤维化（CF）突变分析的范围，确保对目前不进行这种确认性检测的州进行适当的新生儿血斑筛查。该项目与纽约大西洋中部联合会的目标有关，制定了一项区域办法，解决纽约-大西洋中部区域遗传资源分布不均的问题，该区域包括特拉华州、哥伦比亚特区、马里兰州、新泽西州、纽约、宾夕法尼亚州、弗吉尼亚州和西弗吉尼亚州。NYMAC的所有州都对新生儿干血斑进行了一系列遗传和代谢疾病的筛查，其中包括囊性纤维化（CF），但该地区约有一半的新生儿人口无法常规获得囊性纤维化的CFTR突变分析。1

DESCRIPTION (provided by applicant): The goal of this project is to improve the efficacy of screening for Cystic fibrosis (CF) within Region 2, the New York Mid-Atlantic Consortium (NYMAC) for Genetic and Newborn Screening Services, by establishing a regional CF-DNA testing laboratory. Cystic fibrosis is one of the 29 Core Conditions listed in the 2006 American College of Medical Genetics (ACMG) Report, Newborn Screening, Toward a Uniform Screening Panel and System.1 [Newborn Screening: Towards a Uniform Screening Panel and System. Genet Med. 2006; 8(5) Suppl: S12-S252.] CF mutational testing has been recommended and implemented in about half of US states. States that have not implemented CF mutational testing, many being mandatory two-specimen states, may be unable to do so because the recent downturn in the economic environment has prevented any further enhancements to their newborn screening (NBS) systems. By providing free access to CF-DNA mutational testing within the region, we will be able to confirm primary IRT testing and reduce false-positive results. Positive predictive values will improve and the need for sweat testing will be minimized within the region. To attain this goal, a vendor will be selected that has a readily available product with a wide range of mutations covering ethnic groups common to the Northeast US, a limited front end expenditure, and processing that will fit into the present NBS workload. States have been queried, and four states in the NYMAC region have the potential to benefit from the services: Delaware, Maryland, New Jersey and Virginia. Three of these states are performing CF testing using an IRT/IRT algorithm and one is performing IRT followed by CF-DNA testing for F508 only. The Delaware Public Health Laboratory (DPHL) will perform method validation, employ a contract molecular biologist, provide laboratory space, develop a timeline, obtain and install necessary equipment, assure training, and develop the workflow and reporting systems necessary to make this project successful. At the same time this project will explore the effectiveness of centralizing this testing in the NYMAC region. PUBLIC HEALTH RELEVANCE: This project addresses "Healthy People 2010" priority area of maternal, infant, and child health to reduce fetal and infant deaths and to ensure appropriate newborn bloodspot screening by widening the scope of availability of cystic fibrosis (CF) mutation analysis to states who presently do not perform this confirmatory testing. This project is relevant to the goals of the New York Mid-Atlantic Consortium (NYMAC) by developing a regional approach to address the maldistribution of genetic resources in the New York-Mid-Atlantic region, which includes Delaware, District of Columbia, Maryland, New Jersey, New York, Pennsylvania, Virginia and West Virginia. All states in NYMAC screen newborn dried blood spots for a panel of genetic and metabolic diseases which includes cystic fibrosis (CF) but about half of the newborn population in this area does not have routine access to CFTR mutation analysis for cystic fibrosis. 1