![]() Another group of patients with missense mutations in the RAG1 or RAG2 genes does not show the typical clinical features of OS, including generalized eczema, lymphadenopathy, and hepatosplenomegaly ( 5). However, they typically lack B cells, and despite the unexplained presence of high levels of IgE, no antigen-specific antibody responses can be detected. In contrast to patients with complete loss-of-function mutations and complete lack of T and B cells, these patients retain partial V(D)J recombination activity and can generate a substantial number of oligoclonal T cells. These T cells may be due to either materno-fetal transfusion ( 2) or hypomorphic mutations that allow residual function of the affected protein and thus partial T and B cell differentiation.Īn example of SCID patients with partial T cell differentiation are patients with Omenn syndrome (OS) ( 3), the majority of which have hypomorphic mutations in recombinase activating gene 1 ( RAG1) or RAG2 ( 4, 5). In a few SCID patients, however, T cells remain detectable in peripheral blood, rendering the clinical diagnosis more difficult. Depending on the gene affected, patients present with complete absence of T and B cells or, in most cases, with the absence of T cells ( 2). SCID is the common phenotypic presentation of a range of genetic disorders ( 1). This report describes a new phenotype of RAG deficiency and shows that the ability to form specific antibodies does not exclude the diagnosis of SCID. The patient carried the homozygous hypomorphic R561H RAG1 mutation leading to reduced V(D)J recombination but lacked all clinical features characteristic of Omenn syndrome. ![]() These observations are compatible with 2 non–mutually exclusive explanations for the γδ T cell predominance: a developmental advantage and infection-triggered, antigen-driven peripheral expansion. Several γδ T cell clones displayed reactivity against CMV-infected cells. Analysis at a clonal level and TCR complementarity-determining region–3 spectratyping for γδ T cells revealed a diversified oligoclonal repertoire with predominance of cells expressing a γ4-δ3 TCR. The patient had severely reduced levels of oligoclonal T cells expressing the αβ TCR but surprisingly normal numbers of T cells expressing the γδ TCR. Memory B cells were detected and antibodies were produced not only against some vaccines and infections, but also against autoantigens. We describe here a patient with a clinical and molecular diagnosis of recombinase activating gene 1–deficient ( RAG1-deficient) SCID, who produced specific antibodies despite minimal B cell numbers.
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