A novel mutation in TRAC in a patient with abnormal newborn screening for severe combined immunodeficiency

Abstract

Background: The T cell receptor (TCR) α subunit plays a key role in the TCR structure and its function. Biallelic mutations in the TCR-α subunit constant gene (TRAC) obliterated T cell receptor expression and results in immunodeficiency. TRAC deficiency presents at infancy or childhood with repeated viral and bacterial infections, enlarged liver, spleen, and lymph nodes as well as autoimmune features and lymphoma (OMIM #615387).
 Aim: To broaden the genotypic and phenotypic spectrum of TRAC deficiency.
 Methods: Case report of a patient with severe combined immunodeficiency (SCID) due to a novel autosomal recessive mutation in TRAC. 
 Results: Our patient was identified at 13 days of life due to abnormal T cell receptor excision circle levels detected in newborn screening (NBS). Immune evaluation revealed profound lymphopenia, depressed responses to the mitogen PHA and a skewed T cell repertoire, all consistent with SCID. The patient was found to carry a novel homozygous mutation in the TRAC gene. 
 Conclusion: A novel homozygous mutation in the TRAC gene caused profound T cell lymphopenia and aberrant in vitro mitogenic response, the hallmarks of SCID. 
 
 Statement of Novelty: TCR-alpha chain (TRAC) deficiency is a rare and relatively new condition and not very well defined. We herein report a novel mutation in TRAC resulting in SCID.