Development / Validation of 2nd Tier NGS for SCID NBS

 描述（由申请人提供）：2010年9月，纽约成为第四个通过量化T细胞受体切除环（TRECs）进行新生儿重症联合免疫缺陷（SCID）筛查的州。有几种类型的SCID，它们是由许多不同基因的突变引起的，但具有功能性T细胞低或缺乏的共同特征。TRECs是T细胞正常生产过程中形成的独特DNA副产物。TREC定量可用于SCID新生儿筛查，因为低或不存在TREC可指示潜在的T细胞缺陷，包括SCID和其他免疫病症。TREC测定用于鉴定患有经典SCID的婴儿的有效性已经得到充分确立。然而，尚未研究第二层下一代测序测定的可行性和有用性。在获得知情同意后，该项目的目标包括识别低TRECs婴儿的特定基因和突变，跟踪其临床结果并开发患者教育材料。将使用两个下一代测序平台对已知引起SCID的几个基因进行突变分析。将收集患者数据，以确定基因型数据是否对诊断、遗传咨询和评估婴儿的SCID临床护理重要。该项目的推广和教育部分将包括组织一个婴儿经筛查为SCID阳性的父母小组，并利用他们独特的视角创建教育资源。该项目在国家一级具有相关性，因为各州继续将TREC分析添加到其新生儿筛查小组中。在这个项目结束时，将提出一个模型，供其他国家进行成本效益的基因分析。该项目还将收集质量保证标本，以协助疾病预防控制中心实现其目标，为各州提供测试开发和持续质量保证和质量改进的材料。

 DESCRIPTION (provided by applicant): In September 2010, New York became the fourth state to perform newborn screening for severe combined immunodeficiency (SCID) by quantifying T-cell receptor excision circles (TRECs). There are several types of SCID, which are caused by mutations in many different genes, but have a common feature of low or absent functional T-cells. TRECs are a unique DNA byproduct formed during the normal process of T-cell production. TREC quantification can be used for SCID newborn screening because low or absent TRECs may be indicative of an underlying T-cell deficiency, including SCID and other immune disorders. The validity of the TREC assay for identifying infants with classic SCID has been well established. However, the feasibility and usefulness of a second tier next generation sequencing assay has not been studied. After obtaining informed consent, the goals of this project include identification of the specific genes and mutations in infants with low TRECs, tracking their clinical outcomes and developing materials for patient education. Mutation analysis of several genes that are known to cause SCID will be performed using two next generation sequencing platforms. Patient data will be collected to determine whether the genotype data is important for the diagnosis, genetic counseling and resulting clinical care of infants being evaluated for SCID. The outreach and education component of this project will include organizing a group of parents whose infants screened positive for SCID, and using their unique perspective to create educational resources. This project is relevant on a national level because states continue to add TREC analysis to their newborn screening panels. At the conclusion of this project, a model for other states to perform cost- effective gene analysis will be presented. The project will also enable collection of quality assurance specimens to assist the CDC in its goal to provide states with materials for test development and ongoing quality assurance and quality improvement.