Development / Validation of 2nd Tier NGS for SCID NBS



 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.