title: 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 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.
authors.affiliation: Department of Medical Biology, Acibadem University Faculty of Medicine, Istanbul, Turkey. altioke@gmail.com
authors.forename: Ender
authors.initials: E
authors.lastname: Altiok
authors.forename: Figen
authors.initials: F
authors.lastname: Aksoy
authors.forename: Yıldız
authors.initials: Y
authors.lastname: Perk
authors.forename: Fulya
authors.initials: F
authors.lastname: Taylan
authors.forename: Peter W
authors.initials: PW
authors.lastname: Kim
authors.forename: Barbaros
authors.initials: B
authors.lastname: Ilıkkan
authors.forename: Gülten Turkkani
authors.initials: GT
authors.lastname: Asal
authors.forename: Raphaela
authors.initials: R
authors.lastname: Goldbach-Mansky
authors.forename: Ozden
authors.initials: O
authors.lastname: Sanal
mesh_terms: D003241:Consanguinity; D017809:Fatal Outcome; D005260:Female; D005313:Fetal Death; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D007231:Infant, Newborn; D053590:Interleukin 1 Receptor Antagonist Protein / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D053582:Interleukin-1alpha / Q000276:immunology / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D009154:Mutation / Q000276:immunology*; D017472:Receptors, Interleukin-1 / Q000276:immunology / Q000378:metabolism; D035781:Siblings; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D014421:Turkey
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D017472:Receptors, Interleukin-1