Multisystem Anomalies in Severe Combined Immunodeficiency with Mutant BCL11B

Screening of newborns identified an infant with immune deficiency and multisystem developmental defects. Sequencing revealed a heterozygous BCL11B mutation. Mechanistic studies showed that the mutant was a dominant negative that prevented the normal allele from functioning. Population-based screening of newborns for severe combined immunodeficiency (SCID) involves the quantification of blood levels of T-cell–receptor excision circles (TRECs), which are DNA by-products of T-cell–receptor rearrangement that indicate thymic production of naive T cells. 1 Inadequate TREC levels prompt immunologic investigation to diagnose SCID before infections occur, which permits the timely initiation of therapy; therapy usually involves allogeneic hematopoietic stem-cell transplantation from a healthy donor. 2 In addition to enhancing the efficacy of treatment, 2 , 3 newborn screening can reveal previously unknown causes of T-cell lymphopenia. 1 , 4 – 7 Whole-exome sequencing in persons with rare disorders of immunity has led to the identification . . .