Publication Date
12-1-2022
Journal
The Journal of Allergy and Clinical Immunology
DOI
10.1016/j.jaci.2022.08.005
PMID
35987349
PMCID
PMC9742176
PubMedCentral® Posted Date
12-1-2023
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Infant, Newborn, Child, Humans, Genomics, Receptors, Antigen, T-Cell, T-Lymphocytes, T cell lymphopenia, FOXI3, T-cell receptor excision circles
Abstract
BACKGROUND: Newborn screening can identify neonatal T-cell lymphopenia through detection of a low number of copies of T-cell receptor excision circles in dried blood spots collected at birth. After a positive screening result, further diagnostic testing is required to determine whether the subject has severe combined immunodeficiency or other causes of T-cell lymphopenia. Even after thorough evaluation, approximately 15% of children with a positive result of newborn screening for T-cell receptor excision circles remain genetically undiagnosed. Identifying the underlying genetic etiology is necessary to guide subsequent clinical management and family planning.
OBJECTIVE: We sought to elucidate the genetic basis of patients with T-cell lymphopenia without an apparent genetic diagnosis.
METHODS: We used clinical genomic testing as well as functional and immunologic assays to identify and elucidate the genetic and mechanistic basis of T-cell lymphopenia.
RESULTS: We report 2 unrelated individuals with nonsevere T-cell lymphopenia and abnormal T-cell receptor excision circles who harbor heterozygous loss-of-function variants in forkhead box I3 transcription factor (FOXI3).
CONCLUSION: Our findings support the notion that haploinsufficiency of FOXI3 results in T-cell lymphopenia with variable expressivity and that FOXI3 may be a key modulator of thymus development.
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Allergy and Immunology Commons, Medical Genetics Commons, Medical Immunology Commons, Pediatrics Commons
