{Reference Type}: Journal Article
{Title}: FOXI3 haploinsufficiency contributes to low T-cell receptor excision circles and T-cell lymphopenia.
{Author}: Ghosh R;Bosticardo M;Singh S;Similuk M;Delmonte OM;Pala F;Peng C;Jodarski C;Keller MD;Chinn IK;Groves AK;Notarangelo LD;Walkiewicz MA;Chinen J;Bundy V;
{Journal}: J Allergy Clin Immunol
{Volume}: 150
{Issue}: 6
{Year}: 12 2022
{Factor}: 14.29
{DOI}: 10.1016/j.jaci.2022.08.005
{Abstract}: 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.<BR>We sought to elucidate the genetic basis of patients with T-cell lymphopenia without an apparent genetic diagnosis.<BR>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.<BR>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).<BR>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.