Deficiency of the IL-1 Receptor Antagonist (DIRA)
DIRA, deficiency of the IL-1 receptor antagonist, is a monogenic autosomal recessive autoinflammatory disease that presents with systemic inflammation, pustulosis, sterile osteomyelitis, and osteolytic lesions and is caused by loss-of-function mutations in IL1RN, the gene that encodes the IL-1 receptor antagonist (IL-1Ra) (MIM#612852).
Introduction and Background
At a time when whole exome sequencing was not yet available, the diagnosis of sporadic diseases required a candidate gene approach. DIRA was in fact discovered in two patients who had complete responses to empirically administered IL-1 blocking treatments with recombinant IL-1 receptor antagonist, anakinra, which strongly suggested an IL-1-mediated disease, and resulted in a candidate screen of genes in the IL-1/inflammasome pathway that eventually led to finding “the needle in the haystack” (Reddy et al. 2009; Aksentijevich...
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