ABSTRACT
The most common causes of congenital neutropenia are mutations in the ELANE (Elastase, Neutrophil Expressed) gene (19p13.3), mostly in exon 5 and the distal portion of exon 4, which result in different clinical phenotypes of neutropenia. Here, we report two pathogenic mutations in ELANE, namely, c.607G>C (p.Gly203Arg) and a novel variant c.416C>G (p.Pro139Arg), found in two Mexican families ascertained via patients with congenital neutropenia who responded positively to the granulocyte colony-stimulating factor (G-CSF) treatment. These findings highlight the usefulness of identifying variants in patients with inborn errors of immunity for early clinical management and the need to rule out mosaicism in noncarrier parents with more than one case in the family.
Subject(s)
Neutropenia , Humans , Congenital Bone Marrow Failure Syndromes/genetics , Leukocyte Elastase/genetics , Mutation , Neutropenia/congenitalABSTRACT
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by Salmonella, as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in IL12RB1 (n = 13), IFNGR1 (n = 3), and IFNGR2 (n = 1) genes. Interleukin-12Rß1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection.
Subject(s)
Mycobacterium Infections , Mycobacterium bovis , Male , Female , Humans , Retrospective Studies , BCG Vaccine , Genetic Predisposition to Disease , Mexico/epidemiology , Receptors, Interleukin-12/genetics , Mycobacterium Infections/epidemiology , Mycobacterium Infections/geneticsSubject(s)
Humans , Child, Preschool , Protein-Losing Enteropathies , Protein-Losing Enteropathies/diagnosis , Protein-Losing Enteropathies/etiology , Tuberculosis, Gastrointestinal , Tuberculosis, Gastrointestinal/complications , Tuberculosis, Gastrointestinal/diagnosis , Abdominal Pain , Inpatients , Gastroenterology , Diarrhea , AstheniaABSTRACT
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.
