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In 2009, Goldbach-Mansky and colleagues described an autosomal-recessive autoinflammatory disorder known as deficiency of the interleukin 1 (IL-1) receptor antagonist (DIRA)(Fig. 1). 1–6 DIRA is caused by homozygous loss of function mutations in IL1RN, the gene encoding the IL-1 receptor antagonist. Mutations lead to unopposed IL-1 signaling and resultant uncontrolled life-threatening systemic inflammation. Heterozygous carriers of loss of function mutations in IL1RN seem to be asymptomatic. 1–6 Fewer than 20 cases from the

United States, Canada, the Netherlands, Brazil, and Puerto Rico have been described. Firstgeneration mutations in these distinct geographic populations are believed to be founder mutations. The allele frequencies of the founder mutations in Newfoundland and Puerto Rico are estimated at 0.2% and 1.3%, respectively. DIRA is characterized by perinatal-onset pustular dermatitis …