Abstract
Severe combined immunodeficiencies (SCID) comprise a spectrum of genetic defects that involve both humoral and cellular immunities. Defects in recombinating activating gene 1 (RAG1), RAG2, Artemis, or LIG4 can disrupt V(D)J recombination. Defective V(D)J recombination of the T and B cell receptors is responsible for T−B−NK+SCID. Amorphic mutations in RAG1 and RAG2 cause T−B−NK+SCID, whereas hypomorphic mutations cause an immunodeficency characterized by oligoclonal expansion of TCRγδ T cells, severe CMV infection and autoimmunity. First patient is a typical T−B−NK+SCID with clinical and immunologic findings while the second is atypical with normal immunoglobulin levels, CD4 lymphopenia, elevated TCRγδ T cells, persistent CMV infection, and autoimmune hemolytic anemia. These cases are presented to emphasize that mutations in RAG1 gene may lead to a diverse spectrum of clinical and immunologic findings while hypomorphic mutations may be related with autoimmunity and refractory CMV infection during infancy.
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Acknowledgments
We thank Dr. C Sobacchi in CNR-Istituto Tecnologie Biomediche Segrate, Milan, Italy and Dr. JP de Villartay in INSERM, Hôpital Necker-Enfants Malades, Unité Développement Normal et Pathologique du Système Immunitaire, Paris, France for their invaluable help for the identification of mutations in our patients.
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Karaca, N.E., Aksu, G., Genel, F. et al. Diverse phenotypic and genotypic presentation of RAG1 mutations in two cases with SCID. Clin Exp Med 9, 339–342 (2009). https://doi.org/10.1007/s10238-009-0053-1
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DOI: https://doi.org/10.1007/s10238-009-0053-1