IL2RG: A series of three novel mutations with clinical manifestations

Background: X-linked severe combined immunodeficiency (SCID) is caused by mutations in the IL2RG gene and classically presents with absent T cells and natural killer (NK) cells. Mutational analysis has contributed to the understanding of this gene. Methods: The primary immunodeficiency (PID) registry was reviewed for patients with SCID with novel IL2RG mutations. The clinical phenotype was assessed using a retrospective chart review. Results: We describe 3 novel mutations in the IL2RG. The first was a guanine to adenine substitution at position 215 (c.215 G > A) in exon 2 leading to a cysteine to tyrosine substitution at position 72 (p.Cys72Tyr), with a typical T− B+ NK− phenotype. The second was a deletion of thymine at position 618 and adenine at position 619 (c.618_619TA) in exon 5, leading to a frameshift at the 206 amino acid (p.His206fs). The phenotype was characterized by a classic SCID presentation and immunophenotyping revealed a low number of absolute lymphocytes with mostly B cells, low levels of immunoglobulins, as well as very low NK cells. Finally, the third mutation was a guanine to cytosine substitution at position 341 (c.341 G > C) in exon 3 leading to a glycine to alanine substitution at position 114 (p.Gly114Ala), presenting with a T+ B+ NK+ phenotype. The presence of T and NK cells in IL2RG are discussed in the context of other mutations allowing for T and NK cells in IL2RG mutations, as well as in the setting of maternal engraftment. Conclusion: To the best of our knowledge we describe 3 novel mutations in the IL2RG gene and the associated phenotypes. These mutations illustrate that these patients can have atypical immunological evaluations. Statement of novelty: To the best of our knowledge, this paper describes 3 novel mutations in the IL2RG gene.

Download Full-text

Clinical Manifestations, Mutational Analysis, and Immunological Phenotype in Patients With RAG1/2 Mutations: First Cases Series From Mexico and Description of Two Novel Mutations.

10.21203/rs.3.rs-202390/v1 ◽

2021 ◽

Author(s):

Mario Ernesto Cruz-Munoz ◽

Saul Oswaldo Lugo-Reyes ◽

Nina Pastor ◽

Edith González-Serrano ◽

Marco Yamazaki-Nakashimada ◽

...

Keyword(s):

Mutational Analysis ◽

Severe Combined Immunodeficiency ◽

Clinical Manifestations ◽

Case Series ◽

Missense Mutations ◽

Antigen Receptors ◽

Novel Mutations ◽

Nonsense Mutations ◽

First Case ◽

Immunological Phenotype

Abstract Mutations in Recombinase Activating Genes 1 and 2 (RAG1/2) results 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. Nonsense mutations in RAG1 or RAG2 are associated with the most severe clinical and immunological phenotypes, whereas patients with missense mutations may develop leaky SCID or Omenn syndrome (OS). A group of non-previously recognized 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 previously unidentified variants as causative of pathological manifestations associated to immunodeficiency. This study represents the first case series of RAG1 or RAG2 deficient patients from Mexico and Latin America.

Download Full-text

Children With Partial IgA Deficiency

Clinical Pediatrics ◽

10.1177/0009922811417287 ◽

2011 ◽

Vol 51 (1) ◽

pp. 46-50 ◽

Cited By ~ 5

Author(s):

Aarti Shakkottai ◽

Krishnaveni Bupathi ◽

Ankit P. Patel ◽

Elizabeth Chalom ◽

Suneetha Chamarthi ◽

...

Keyword(s):

Joint Pain ◽

Antinuclear Antibody ◽

Chart Review ◽

Morning Stiffness ◽

Clinical Manifestations ◽

Retrospective Chart Review ◽

Iga Deficiency ◽

Rheumatology Clinic ◽

History Of ◽

Pediatric Rheumatology Clinic

Literature is lacking on partial IgA deficiency. In this study, the authors propose to describe the clinical manifestations of patients with partial IgA deficiency. Methods. The authors conducted a retrospective chart review of 13 patients with partial IgA deficiency followed at the pediatric rheumatology clinic at Robert Wood Johnson Medical School. They looked for the presence of rashes, joint pain, joint swelling, and morning stiffness. The authors also examined charts for a history of frequent infections, allergies, and the presence of elevated antinuclear antibody. Results. Eleven out of the 13 patients complained of joint pain, joint swelling, or morning stiffness. Six patients carried a diagnosis of a definitive rheumatic disease. Four patients suffered from frequent infections and 2 patients reported allergies. Conclusion. Partial IgA deficiency appears to be associated with rheumatic diseases and complaints of joint pain, joint swelling, and morning stiffness. A larger study is needed to confirm these results.

Download Full-text

Limiting γc expression differentially affects signaling via the interleukin (IL)-7 and IL-15 receptors

Blood ◽

10.1182/blood-2006-11-055442 ◽

2007 ◽

Vol 110 (1) ◽

pp. 91-98 ◽

Cited By ~ 9

Author(s):

Christine M Smyth ◽

Samantha L Ginn ◽

Claire T Deakin ◽

Grant J Logan ◽

Ian E Alexander

Keyword(s):

Signal Transduction ◽

B Cells ◽

Nk Cells ◽

Nk Cell ◽

Severe Combined Immunodeficiency ◽

Gamma Chain ◽

Experimental Conditions ◽

Il2rg Gene ◽

The Common ◽

Cell Ontogeny

X-linked severe combined immunodeficiency (SCID-X1) results from mutations in the IL2RG gene, which encodes the common gamma chain (γc) of the receptors for interleukin (IL)-2, 4, 7, 9, 15, and 21. Affected infants typically lack T and natural killer (NK) cells as a consequence of loss of signaling via the IL-7 receptor (IL-7R) and the IL-15R, respectively. In some infants, however, autologous NK cells are observed despite failure of T-cell ontogeny. The mechanisms by which mutations in γc differentially impact T- and NK-cell ontogeny remain incompletely understood. We used SCID-X1 patient–derived EBV-transformed B cells to test the hypothesis that the IL-15R–mediated signaling is preferentially retained as γc expression becomes limiting. Signal transduction via the IL-15R was readily detected in control EBV-transformed B cells, and via the IL-7R when modified to express IL-7Rα. Under the same experimental conditions, patient-derived EBV-transformed B cells expressing trace amounts of γc proved incapable of signal transduction via the IL-7R while retaining the capacity for signal transduction via the IL-15R. An equivalent result was obtained in ED-7R cells modified to express varying levels of γc. Collectively, these results confirm that signal transduction via the IL-15R, and hence NK ontogeny, is preferentially retained relative to the IL-7R as γc expression becomes limiting.

Download Full-text

Klebsiella pneumoniae Orbital Cellulitis: Clinical Manifestations and Outcomes in a Tertiary Medical Center in Taiwan

Journal of Ophthalmology ◽

10.1155/2018/4237573 ◽

2018 ◽

Vol 2018 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Chieh-Hung Yen ◽

Shu-Ya Wu ◽

Yi-Lin Liao

Keyword(s):

Klebsiella Pneumoniae ◽

Chart Review ◽

Medical Center ◽

Clinical Manifestations ◽

Retrospective Chart Review ◽

Skin Wound ◽

Orbital Cellulitis ◽

Ocular Motility ◽

Dental Procedure ◽

Bacterial Cultures

Purpose. To report six cases of Klebsiella pneumoniae orbital cellulitis without preceding endophthalmitis. Method. Retrospective chart review. Results. We reported four females and two males admitted to our hospital for Klebsiella pneumoniae orbital cellulitis proven by computed tomographies and bacterial cultures from May 1995 to March 2017. Proptosis, conjunctival congestion, and chemosis and limitation of ocular motility were present in all six patients. Four patients had decreased visual acuities, and three of them recovered completely after treatment. The origin of the infection was sinus in four patients, skin wound in one patient, and sepsis presumably caused by a dental procedure in one patient. Three of all six patients had underlying diabetes mellitus. Two patients had orbital cellulitis before they were diagnosed of diabetes during hospital stay. Conclusion. Diabetes may be a risk factor of Klebsiella pneumoniae orbital cellulitis, especially for those of nonsinus origin.

Download Full-text