Development / Validation of 2nd Tier NGS for SCID NBS

SCID NBS 的第二层 NGS 的开发/验证

• 批准号: 9137612
• 负责人: MICHELE CAGGANA
• 金额: $ 43.73万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2018-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9137612
• 关键词: Development; Validation; 2nd; Tier; NGS

 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.

 描述（由适用提供）：2010年9月，纽约成为通过量化T细胞受体惊喜电路（TREC）进行严重合并免疫缺陷（SCID）进行新生儿筛查的第四个州。有几种类型的SCID是由许多不同基因突变引起的，但具有低或缺乏功能性T细胞的共同特征。 TREC是在TREC定量期间形成的独特DNA副产物，可以用于SCID新生儿筛查，因为低或缺乏TREC可能表明了潜在的T细胞缺乏，包括SCID和其他免疫疾病。 TREC测定法对鉴定经典SCID的婴儿的有效性已经确定。但是，第二层下一代测序测定的可行性和实用性尚未研究。在获得知情同意后，该项目的目标包括鉴定TREC较低的婴儿的特定基因和突变，跟踪其临床结果和开发患者教育的材料。对几种已知引起SCID的基因的突变分析将使用两个下一代测序平台进行。将收集患者数据，以确定基因型数据对于评估SCID的婴儿的诊断，遗传咨询和导致的临床护理是否重要。该项目的宣传和教育部分将包括组织一群父母，他们的婴儿对SCID的筛查呈阳性，并利用其独特的观点来创造教育资源。该项目在国家一级是相关的，因为各州继续将TREC分析添加到其新生儿筛查小组中。在该项目的结论结束时，将提出其他州进行成本效益的基因分析的模型。该项目还将促进质量保证标本的收集，以协助疾病预防控制中心为州提供测试开发和持续质量保证和质量改进的材料。