Understanding Newborn Screening and T-Cell Receptor Excision Circles
The content discusses the importance of newborn screening, characteristics of disorders, T-cell receptor excision circles (TRECs), and the identification of severe conditions like SCID through TREC assay. It highlights the significance of early detection and treatment, emphasizing the value of high-throughput screening methods and the potential future directions in TREC assays for genetic disease screening.
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Presentation Transcript
Newborn Screening Characteristics of Test Characteristics of Disorders Well characterized pathogenesis Affects a significant number of infants Undetectable by routine examination Result in devastating consequences if not diagnosed/treated early Disease-altering treatment available High sensitivity and specificity Amenable for high- throughput screening Favorable cost-benefit analysis Low risk to infant Means of providing follow up Chase. Curr. Opin. All. Imm. 2010, 10:521 5256
T-Cell Receptor Excision Circles (TRECs) Generation of a unique T-cell receptor (TCR) clone begins by random selection and combination of TCR regions in germ line DNA The excised DNA sequences form a non- replicating episome TREC-positive cells are recent thymic emigrants Chase. Curr. Opin. All. Imm. 2010, 10:521 5256
T-Cell Receptor Excision Circles (TRECs) TRECs can be detected in peripheral blood by quantitative PCR TREC levels correlate with numbers of na ve T- cells Low TREC levels associated with SCID, diGeorge syndrome, congenital lymphopenia Hazenberg. J. Mol. Med. 2001, 79:631 640
T-Cell Receptor Excision Circles (TRECs) 2008: Wisconsin became first state to include TREC quantitation in the newborn screen 2009: The first infant with SCID identified in Massachusetts* 2010: TREC assay added to New York newborn screen * Hale. J. All. Clin. Immunol. 2010, 126:1073 4
TREC Assay Pitfalls and Future Directions Reference ranges have not been established for neonates < 37 weeks corrected gestation Many abnormal TREC results have lead to diagnosis of undefined T-cell immunodeficiencies; without identifying underlying genetic defect optimal management remains uncertain Multi-plex quantitative PCR methods are being developed to screen for additional genetic diseases
