title: The first reported case of compound heterozygous IL1RN mutations causing deficiency of the interleukin-1 receptor antagonist.
abstract: Interleukin-1 receptor antagonist (IL-1Ra) deficiency is a rare autoinflammatory disease involving neonatal onset of pustulosis, periostitis, and sterile osteomyelitis. We report the case of a 2-week-old male who presented with a swollen, erythematous left index finger and elevated serum markers of inflammation. He later developed cyclical fevers, diffuse pustular skin lesions, and thrombus formation. After not responding to broad-spectrum antimicrobial therapy and achieving only moderate success with systemic steroid therapy, he was ultimately treated with recombinant IL-1Ra, anakinra, and experienced significant clinical improvement. Sequencing of his IL1RN gene revealed that the patient was compound heterozygous for a known mutation (E77X) associated with IL-1Ra deficiency and a novel mutation in exon 2 of the gene (c.140delC; p.T47TfsX4). His case highlights IL-1Ra deficiency as an autoinflammatory disease that is distinct from neonatal-onset multisystem inflammatory disease but that also responds well to anakinra. Our patient is the first reported compound heterozygote for E77X and the novel mutation in exon 2 of the gene, the latter of which adds to what will surely be a growing database of pathologic mutations in IL1RN.
authors.affiliation: Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Stenerson
authors.forename: Kevin
authors.initials: K
authors.lastname: Dufendach
authors.forename: Ivona
authors.initials: I
authors.lastname: Aksentijevich
authors.forename: Jillian
authors.initials: J
authors.lastname: Brady
authors.forename: Jared
authors.initials: J
authors.lastname: Austin
authors.forename: Ann M
authors.initials: AM
authors.lastname: Reed
mesh_terms: D018501:Antirheumatic Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005091:Exons / Q000235:genetics; D056660:Hereditary Autoinflammatory Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007231:Infant, Newborn; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics* / Q000627:therapeutic use; D008297:Male; D009154:Mutation / Q000235:genetics*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein