A novel mutation of XXXX in the deficiency of interleukin-1 receptor antagonist syndrome: description of two unrelated cases from Brazil.

@entity1 @entity32 @entity14028 @entity1909 @entity1569 @entity5704 @entity1356 @entity4034 @entity1193 @entity49 @entity70842 @entity1192 @entity4421 @entity1030 @entity8649 @entity62770 @entity35393
OBJECTIVE: Monogenic @entity8649 are disorders of Mendelian inheritance that are characterized by mutations in genes that regulate innate immunity and whose typical features are systemic @entity32 without high-titer autoantibodies or antigen-specific T cells. Skin and @entity4421 in the newborn period have been described in 3 of these autoinflammatory disorders: neonatal-onset multisystem @entity32 , @entity70842 , and deficiency of @entity1193 (DIRA) syndrome. This study was undertaken to present the characteristics of the @entity62770 in 2 cases from Brazil, and describe a novel mutation in @entity1193 . METHODS: Two unrelated Brazilian @entity1 were evaluated for the clinical signs and symptoms of these 3 disorders, and peripheral blood samples were assessed for mutations in @entity5704 , @entity35393 , and @entity1193 by DNA resequencing analysis. A mutation in @entity1193 that encodes a mutant protein was identified, and the expression and function of this mutant protein were compared to those of the wild-type protein. RESULTS: Both @entity1 presented with @entity1909 resembling @entity1569 , recurrent multifocal @entity4034 , and elevation in the levels of acute-phase reactants, all of which are features most consistent with the @entity62770 . @entity1030 was observed in 1 of the @entity1 , and @entity49 was observed in the other @entity1 . Both @entity1 showed a partial response to corticosteroid therapy, and 1 @entity1 experienced an initial improvement of @entity1909 with the use of @entity14028 . Both @entity1 were homozygous for a novel 15-bp (in-frame) deletion on the @entity1193 gene. The mutated protein expressed in vitro had no affinity with the IL-1 receptor, and stimulation of the @entity1 ' cells with recombinant @entity1 @entity1192 or @entity1356 led to oversecretion of proinflammatory cytokines, similar to the findings obtained in previously reported @entity1 . CONCLUSION: The presence of the same homozygous novel mutation in @entity1193 in 2 unrelated Brazilian @entity1 suggests that this genetic variant may be a founder mutation that has been introduced in the Brazilian population.
