Letters to the Editor

Autoimmunity due to RAG deficiency and esti-mated disease incidence in RAG1/2 mutations To the Editor: A growing body of literature demonstrates that recombinase activating gene (RAG1/2) deficiency is seen in patients with autoimmune features and variable immunodeficiency, thus expanding the phenotype beyond T2/B2/natural killer1 severe combined immunodeficiency (SCID) and Omenn syndrome (OS).1,2 Based on data from SCID newborn screening programs in the United States and Puerto Rico, the estimated incidence of SCID is approximately 1:50,000.3 Recent data from California’s SCID newborn screening identified RAG1/2 mutations in 28.6 % of SCID/OS cases, for an incidence of about 1:250,000.4 However, this may not include individuals with less severe phenotypes caused by RAG1/2 defects. We present a family affected by compound heterozygous RAG1 mutations that resulted in a combined immunodeficiency phenotype with autoimmune cytopenias. We performed a population genetic analysis to estimate the incidence of disease caused by RAG1/2 homozygous or compound heterozy-gous mutations and found that the contribution of immuneFIG 1. A, Sanger sequencing chromatogram of parents of the affected children confirms RAG1 mutation carrier status. Arrow indicates mutation position. B, Pedigree of family with RAG1 deficiency. Patient 1 (P1, II.1) and patient 2 (P2, II.4) were affected with autoimmune cytopenias and infections. Het, Heterozy-gous; WT, wild type. C, Multiple sequence alignment of the RAG1 locus with c.2949delA(p.K983NfsX9) mutation. 880 im ter od icr