Mutation screening of the IL-1 receptor antagonist gene in chronic non-bacterial osteomyelitis of childhood and adolescence

Objective Chronic non-bacterial osteomyelitis CNO is an inflammatory disorder of the musculoskeletal system with unknown etiology. In addition to bone inflammation, patients may present with inflammatory involvement of other tissues including, e.g.,skin. Recently, a novel syndrome due to deficiency of interleukin-1 receptor antagonist (IL1RN), DIRA has been identified. Clinically the syndrome is characterized by neonatal onset of pustular dermatosis, periostitis and chronic sterile multifocal osteomyelitis, strongly resembling CNO. Homozygous mutations of IL1RN have been identified and resulted in a truncated protein that is not secreted, hence leaving the action of interleukin-1 unopposed. Methods Because of similar clinical, radiological and histological features of CNO and DIRA, we hypothesized that both disorders might share a common autoinflammatory process. Thus, we searched for the presence of mutations in the interleukin-1 receptor antagonist gene in 60 patients diagnosed with CNO. Results In one patient with chronic multifocal osteomyelitis a heterozygous missense variant: c.281G>T (p.Cys94Phe) was detected. In the other patients only frequent polymorphisms were found. Conclusion Our findings were not able to confirm mutations in IL1RN being an important contributing factor to the pathogenesis of CNO.