Open AccessClinical Manifestations, Mutational Analysis, and Immunological Phenotype in Patients with RAG1/2 Mutations: First Cases Series from Mexico and Description of Two Novel Mutations
Author(s) -
Saúl Oswaldo Lugo Reyes,
Nina Pastor,
Edith González-Serrano,
Marco Antonio YamazakiNakashimada,
Selma SchefflerMendoza,
Laura BerrónRuiz,
Guillermo Wakida,
María NúñezNúñez,
Ana Paola Macías-Robles,
Aidé Tamara StainesBoone,
Edna Venegas-Montoya,
Carmen Aláez-Verson,
Carolina MolinaGaray,
Luis Leonardo FloresLagunes,
Karol CarrilloSánchez,
Julie E. Niemela,
Sergio D. Rosenzweig,
Paul Gaytán,
Jorge Yáñez,
Iván Martínez-Duncker,
Luigi D. Notarangelo,
Sara Espinosa-Padilla,
Mario Ernesto Cruz-Muñoz
Publication year - 2021
Publication title -
journal of clinical immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.739
H-Index - 96
eISSN - 1573-2592
pISSN - 0271-9142
DOI - 10.1007/s10875-021-01052-0
Subject(s) - recombination activating gene , rag2 , biology , missense mutation , phenotype , severe combined immunodeficiency , primary immunodeficiency , mutation , genetics , immunodeficiency , immunology , gene , immune system , recombination
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.