Development / Validation of 2nd Tier NGS for SCID NBS

 描述(申请人提供)：2010年9月，纽约州成为第四个通过量化T细胞受体切除环(TRECs)进行新生儿严重联合免疫缺陷(SCID)筛查的州。有几种类型的SCID，是由许多不同基因的突变引起的，但都有一个共同的特征，即功能低下或缺乏功能的T细胞。TRECs是T细胞正常生产过程中形成的一种独特的DNA副产物。TREC定量可用于SCID新生儿筛查，因为TREC低或缺失可能表明潜在的T细胞缺陷，包括SCID和其他免疫疾病。TREC试验在鉴别典型SCID婴儿方面的有效性已经得到了很好的证实。然而，第二级下一代测序分析的可行性和有用性还没有被研究。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，跟踪他们的临床结果，并开发用于患者教育的材料。将使用两个下一代测序平台对几个已知的导致SCID的基因进行突变分析。将收集患者数据，以确定基因数据是否对正在评估SCID的婴儿的诊断、遗传咨询和由此产生的临床护理重要。该项目的外展和教育部分将包括组织一组婴儿SCID筛查呈阳性的父母，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，因为各州继续在其新生儿筛查小组中增加TREC分析。在本项目结束时，将为其他州进行经济有效的基因分析提供一个模型。该项目还将收集质量保证样本，以协助疾病预防控制中心实现其目标，即向各国提供用于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.