Mutations in recombinase activating genes 1 and 2 (RAG1/2) result in human severe combined immunodeficiency (SCID). The products of these genes are essential for V(D)J rearrangement of the antigen receptors during lymphocyte development. Mutations resulting in null-recombination activity in RAG1 or RAG2 are associated with the most severe clinical and immunological phenotypes, whereas patients with hypomorphic mutations may develop leaky SCID, including Omenn syndrome (OS). A group of previously unrecognized clinical phenotypes associated with granulomata and/or autoimmunity have been described as a consequence of hypomorphic mutations. Here, we present six patients from unrelated families with missense variants in RAG1 or RAG2. Phenotypes observed in these patients ranged from OS to severe mycobacterial infections and granulomatous disease. Moreover, we report the first evidence of two variants that had not been associated with immunodeficiency. This study represents the first case series of RAG1- or RAG2-deficient patients from Mexico and Latin America.
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The authors would like to thank the patients and their families for participating in this study.
MECM is supported by Consejo Nacional de Ciencia y Tecnología (CONACYT 281854).
LDN is supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
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This study and the written consent forms were approved by the local ethics committees in accordance with the Declaration of Helsinki (Protocols 00165 and 049/2013).
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Lugo-Reyes, S.O., Pastor, N., González-Serrano, E. et al. Clinical Manifestations, Mutational Analysis, and Immunological Phenotype in Patients with RAG1/2 Mutations: First Cases Series from Mexico and Description of Two Novel Mutations. J Clin Immunol 41, 1291–1302 (2021). https://doi.org/10.1007/s10875-021-01052-0
- Primary immunodeficiencies
- T lymphocytes
- Omenn syndrome