A novel mutation in the interleukin-1 receptor antagonist associated with intrauterine disease onset

Abstract Deficiency of the IL-1 receptor antagonist (DIRA) is a recently described rare autoinflammatory disease, caused by loss of function mutations in IL1RN leading to the unopposed activation of the IL-1 pathway. We describe a novel nonsense mutation in the IL1RN gene, associated with early intr...

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Bibliographic Details
Published in:Clinical immunology (Orlando, Fla.) Fla.), 2012-10, Vol.145 (1), p.77-81
Main Authors: Altiok, Ender, Aksoy, Figen, Perk, Yıldız, Taylan, Fulya, Kim, Peter W, Ilıkkan, Barbaros, Asal, Gülten Turkkani, Goldbach-Mansky, Raphaela, Sanal, Ozden
Format: Article
Language:English
Subjects:
Allergy and Immunology
Antibiotics
Autoinflammatory syndrome
Biological and medical sciences
Consanguinity
Deficiency of interleukin-1 receptor antagonist
Fatal Outcome
Female
Fetal Death
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Humans
Immunodeficiencies
Immunodeficiencies. Immunoglobulinopathies
Immunodeficiency
Immunologic Deficiency Syndromes - genetics
Immunologic Deficiency Syndromes - immunology
Immunopathology
Infant, Newborn
Infection
Interleukin 1
Interleukin 1 receptor antagonist
Interleukin 1 Receptor Antagonist Protein - deficiency
Interleukin 1 Receptor Antagonist Protein - genetics
Interleukin 1 Receptor Antagonist Protein - immunology
Interleukin 1 receptors
Interleukin-1alpha - immunology
Interleukin-1alpha - metabolism
Intrauterine onset
Male
Medical sciences
Models, Molecular
Mutation - immunology
Nonsense mutation
Receptors, Interleukin-1 - immunology
Receptors, Interleukin-1 - metabolism
Siblings
Signal transduction
Signal Transduction - genetics
Signal Transduction - immunology
Turkey
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Description
Summary:Abstract Deficiency of the IL-1 receptor antagonist (DIRA) is a recently described rare autoinflammatory disease, caused by loss of function mutations in IL1RN leading to the unopposed activation of the IL-1 pathway. We describe a novel nonsense mutation in the IL1RN gene, associated with early intrauterine onset, death and multiorgan involvement in a prematurely born baby. The protein prediction model indicated that the novel Q119X mutation would result in a nonfunctional protein by impairing the ability of the IL-1Ra to bind and antagonize signaling through the IL-1R. Since the disorder may mimic severe bacterial infections and the treatment with anakinra is life saving, we intend to raise awareness of the syndrome and the possibility of a founder mutation that may lead to the diagnosis of additional cases in Turkey. The clinical suspicion of DIRA is critical to avoid improper management of the patients with antibiotics alone and death from multiorgan failure.
ISSN:1521-6616
1521-7035
DOI:10.1016/j.clim.2012.08.003